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1.
Protein & Cell ; (12): 788-809, 2021.
Article in English | WPRIM | ID: wpr-922475

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.


Subject(s)
Adult , Aged , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins/metabolism , /metabolism , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Middle Aged , Neoplasm Staging , Prognosis , Protein Binding , RNA, Small Interfering/metabolism , Survival Analysis , Tumor Burden , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , beta Catenin/metabolism
2.
Article in English | WPRIM | ID: wpr-921383

ABSTRACT

Head and neck cancer is the seventh common cancer in the world, and various existing treatment strategies provide modest benefit for most patients with head and neck cancer. Meanwhile, therapeutic strategies lacking molecular typing significantly hinder the development of individualized treatment for head and neck cancer. In recent years, connected by preclinical models, the novel ideal has gradually reached a consensus in terms of facilitating inter-transformation of clinical problems and basic achievements. As a bridge between basic research and clinical transformation, patient-derived xenografts (PDX) models precisely replicate genetic characteristics and tumor evolution, which are displaying great vitality in elucidating the mechanism of tumorigenesis and progression. Moreover, cohorts composed of several PDX models highlight the unique advantages of mice for drug screening and biomarker analysis for patients. This ideal preclinical model explores potential treatment strategies suited the ethical standards as much as possible for patients.


Subject(s)
Animals , Disease Models, Animal , Head and Neck Neoplasms , Heterografts , Humans , Mice , Xenograft Model Antitumor Assays
3.
Article in Chinese | WPRIM | ID: wpr-878839

ABSTRACT

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 μmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.


Subject(s)
Animals , Capsules , Carcinoma, Hepatocellular , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Fluorouracil , Heterografts , Liver Neoplasms , Mice , Mice, Nude , Vascular Endothelial Growth Factor A , Xenograft Model Antitumor Assays
4.
Chinese Journal of Biotechnology ; (12): 2162-2170, 2020.
Article in Chinese | WPRIM | ID: wpr-878475

ABSTRACT

We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.


Subject(s)
4-1BB Ligand/metabolism , Cell Line, Tumor , Genetic Engineering , Humans , Inducible T-Cell Co-Stimulator Protein/metabolism , Multiple Myeloma/therapy , Signal Transduction , T-Lymphocytes/chemistry , Xenograft Model Antitumor Assays
5.
Article in Chinese | WPRIM | ID: wpr-880764

ABSTRACT

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.


Subject(s)
Animals , Bile Duct Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/genetics , Cytoskeletal Proteins , Heterografts , Humans , Imidazoles , Mice , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Pyridazines , Receptor, Fibroblast Growth Factor, Type 2 , Xenograft Model Antitumor Assays
6.
Chinese Journal of Biotechnology ; (12): 979-991, 2020.
Article in Chinese | WPRIM | ID: wpr-826878

ABSTRACT

Adoptive immunotherapy based on chimeric antigen receptor-modified T cells (CAR-T) is one of the most promising strategies to treat malignant tumors, but its application in solid tumors is still limited. Glypican-3 (GPC3) is a meaningful diagnostic, therapeutic, and prognostic biomarker for hepatocellular carcinoma (HCC). The second/third generation GPC3-targeted CAR-T cells are generated to treat HCC. In order to improve the therapeutic effect, we constructed a fourth-generation lentiviral vector to express GPC3 CAR, human interleukin-7 (IL-7) and CCL19. Then the lentiviral vector and packaging plasmids were co-transfected into HEK293T cells to generate CAR lentiviral particles. Human T lymphocyte cells were transduced with CAR lentiviral to develop the fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19). In vitro, we used cell counting, transwell assay, luciferase bioluminescence assay and flow cytometry to compare the proliferation, chemotaxis, cytotoxicity and subtype distribution between GPC3-BBZ-7×19 CAR-T cells and the second generation GPC3-targeted CAR-T cells (GPC3-BBZ). In vivo, we established GPC3-positive HCC xenograft model in immunodeficient mice, then untransduced T cells (non-CAR-T) or GPC3-BBZ-7×19 CAR-T cells were injected. Tumor growth in mice was observed by bioluminescence imaging. Results showed that compared with GPC3-BBZ CAR-T, GPC3-BBZ-7×19 CAR-T cells had stronger proliferation, chemotactic ability, and higher composition of memory stem T cells (Tscm) (P values<0.05). However, there were no significant difference in cytotoxicity and cytokine secretion between them. In addition, GPC3-BBZ-7×19 CAR-T cells could significantly eliminate GPC3-positive HCC xenografts established in immunodeficient mice. Therefore, the fourth-generation GPC3-targeted CAR-T cells (secreting IL-7 and CCL19) are expected to be more durable and effective against HCC and produce tumor-specific memory, to provide a preclinical research basis for future clinical trials.


Subject(s)
Animals , Carcinoma, Hepatocellular , Cell Line, Tumor , Chemokine CCL19 , Metabolism , Glypicans , Metabolism , HEK293 Cells , Humans , Interleukin-7 , Metabolism , Lentivirus , Genetics , Liver Neoplasms , Mice , Receptors, Chimeric Antigen , Metabolism , T-Lymphocytes , Metabolism , Xenograft Model Antitumor Assays
7.
Article in Chinese | WPRIM | ID: wpr-828908

ABSTRACT

OBJECTIVE@#To investigate the difference of tumor formation in different mouse strains bearing patient-derived xenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study of individualized treatment of ESCC.@*METHODS@#The tumor tissues collected from 22 ESCC patients were used to establish tumor-bearing mouse models in B-NDG (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formation time were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing were carried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues.@*RESULTS@#The tumor-bearing models were established successfully in both NSG mice (50%, 11/22) and BALB/c nude mice (18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 91.67 days, < 0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identical to those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater genetic similarity to the patients' tumors than those in BALB/c nude mice ( < 0.0001).@*CONCLUSIONS@#Mouse models bearing xenografts of patient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the former mouse strain can be more reliable.


Subject(s)
Animals , Cell Line, Tumor , Cell Proliferation , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Heterografts , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Xenograft Model Antitumor Assays
8.
Braz. j. med. biol. res ; 53(4): e9114, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089357

ABSTRACT

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.


Subject(s)
Humans , Animals , Male , Female , Middle Aged , Carcinoma, Hepatocellular/metabolism , Dipeptidyl Peptidase 4/metabolism , Liver Neoplasms/metabolism , Prognosis , Immunohistochemistry , Biomarkers, Tumor , Follow-Up Studies , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Xenograft Model Antitumor Assays , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Neoplasm Recurrence, Local
9.
Biol. Res ; 53: 14, 2020. graf
Article in English | LILACS | ID: biblio-1100920

ABSTRACT

BACKGROUND: Previous studies have shown that long noncoding RNA (IncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this IncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1). METHODS: Thirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo. RESULTS: LINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis. CONCLUSION: Knockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR- 490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.


Subject(s)
Humans , Animals , Male , Stomach Neoplasms/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Cell Movement , Cell Survival , Apoptosis , Xenograft Model Antitumor Assays , MicroRNAs/genetics , Cell Line, Tumor/metabolism , Epithelial Cells/metabolism , RNA, Long Noncoding/genetics , Carcinogenesis/metabolism , Luciferases/metabolism , Mice, Inbred BALB C
10.
Frontiers of Medicine ; (4): 83-93, 2019.
Article in English | WPRIM | ID: wpr-771264

ABSTRACT

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.


Subject(s)
Animals , Antibodies, Monoclonal , Pharmacology , Antineoplastic Agents, Immunological , Pharmacology , Caco-2 Cells , Cell Proliferation , Colorectal Neoplasms , Therapeutics , ErbB Receptors , Genetics , Allergy and Immunology , Female , HT29 Cells , Humans , Mice , Mice, Inbred BALB C , Mutation , Xenograft Model Antitumor Assays
11.
Frontiers of Medicine ; (4): 57-68, 2019.
Article in English | WPRIM | ID: wpr-771260

ABSTRACT

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.


Subject(s)
Animals , Carcinoma, Non-Small-Cell Lung , Allergy and Immunology , Therapeutics , Cell Line, Tumor , ErbB Receptors , Allergy and Immunology , Metabolism , Female , Humans , Immunotherapy, Adoptive , Methods , Lung Neoplasms , Allergy and Immunology , Therapeutics , Mice , Mice, Inbred NOD , Receptors, Chimeric Antigen , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology , Xenograft Model Antitumor Assays
12.
Chinese Medical Journal ; (24): 311-318, 2019.
Article in English | WPRIM | ID: wpr-774849

ABSTRACT

BACKGROUND@#The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH).@*METHODS@#All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence.@*RESULTS@#Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation.@*CONCLUSION@#The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.


Subject(s)
Animals , Antineoplastic Agents , Therapeutic Uses , Blotting, Western , Bridged Bicyclo Compounds, Heterocyclic , Therapeutic Uses , Carcinoma, Hepatocellular , Drug Therapy , General Surgery , Cell Cycle , Cell Proliferation , Chromosomal Proteins, Non-Histone , Electrophoresis, Polyacrylamide Gel , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Liver Neoplasms , Drug Therapy , General Surgery , Liver Regeneration , Physiology , Mice , Mice, Inbred C57BL , Real-Time Polymerase Chain Reaction , Sarcosine , Therapeutic Uses , Xenograft Model Antitumor Assays
13.
Article in English | WPRIM | ID: wpr-776609

ABSTRACT

OBJECTIVE@#To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models.@*METHODS@#PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review.@*RESULTS@#CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate.@*CONCLUSION@#CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.


Subject(s)
Animals , Drugs, Chinese Herbal , Therapeutic Uses , Mice , Osteosarcoma , Drug Therapy , Publication Bias , Risk Factors , Tumor Burden , Xenograft Model Antitumor Assays
14.
Article in Chinese | WPRIM | ID: wpr-772338

ABSTRACT

BACKGROUND@#Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment.@*METHODS@#Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy.@*RESULTS@#Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67).@*CONCLUSIONS@#The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.


Subject(s)
Animals , Antineoplastic Combined Chemotherapy Protocols , Pharmacology , Cisplatin , Disease Models, Animal , Drug Resistance, Neoplasm , Etoposide , Female , Humans , Interleukin Receptor Common gamma Subunit , Genetics , Lung Neoplasms , Drug Therapy , Metabolism , Pathology , Mice, Inbred BALB C , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Small Cell Lung Carcinoma , Drug Therapy , Metabolism , Pathology , Transplantation, Heterologous , Methods , Xenograft Model Antitumor Assays
15.
Food Sci. Technol (SBCTA, Impr.) ; 38(1): 106-111, Jan.-Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-892237

ABSTRACT

Abstract The present study investigated the effects of curcumin (Cur) on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control), 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05). The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05), and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05). Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.


Subject(s)
Humans , Animals , Female , Mice , Uterine Cervical Neoplasms , Curcumin , Heterografts , Plants, Medicinal , Xenograft Model Antitumor Assays , Polyphenols , Mice, Nude
16.
Food Sci. Technol (SBCTA, Impr.) ; 38(1): 78-83, Jan.-Mar. 2018. tab
Article in English | LILACS | ID: biblio-892251

ABSTRACT

Abstract This study investigated the inhibitory effect of Dendrobium officinale polysaccharide (DOPA) on human gastric cancer cell SGC-7901 xenografts in nude mice. The nude mice with SGC-7901 xenografts were randomly divided into model, 5-fluorouracil (5-Fu), low-dose DOPA, middle-dose DOPA and high-dose DOPA group. The later four groups were intragastrically administrated with 100, 200 and 400 mg·kg-1·day-1 DOPA, 400 mg·kg-1·day-1 5-Fu and normal saline, respectively. After treatment for 20 days, the tumor inhibition rate of in high-dose DOPA group was basically equivalent to 5-Fu group. Compared with 5-Fu, DOPA had no obvious toxic side effect on spleen or thymus indexes, routine blood indexes or liver and kidney functions of nude mice. Compared with model group, the serum tumor necrosis factor-α and interleukin-2 levels in middle- and high-dose DOPA group were significantly increased (P < 0.05), Bax protein expression was significantly increased (P < 0.05), and Bcl-2 protein expression was significantly decreased (P < 0.05). DOPA can inhibit the growth of SGC-7901 cell xenografts in nude mice. The mechanism may be related to its increase of serum TNF-α and IL-2 levels, up-regulation of Bax protein expression and down-regulation of Bcl-2 protein expression.


Subject(s)
Humans , Animals , Mice , Stomach Neoplasms , Xenograft Model Antitumor Assays , Plants, Medicinal , Polysaccharides , Stomach Neoplasms/therapy , Dendrobium , Heterografts , Mice, Nude
17.
Article in English | WPRIM | ID: wpr-776650

ABSTRACT

OBJECTIVE@#To investigate the anti-leukemia effect of total saponins of Rubus parvifolius L. (TSRP) on K562 cell xenografts in nude mice and the mechanisms of action.@*METHODS@#The K562 cell xenografts in nude mice were established, and then randomly divided into 5 groups, the control group, the cytosine arabinoside group(Ara-c) and 3 TSRP groups (20, 40 and 100 mg/kg). The tumor volume and mass of each group of nude mice were measured and the anti-tumor rates of TSRP were calculated subsequently. The apoptosis status of tumor cells was detected by hematoxylin-eosin (HE) and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining analysis. Finally, the activities of apoptosis related signaling of signal transducer and activator of transcription 3 (STAT3), eukaryotic initiation factor 4E (eIF4E) and B-cell lymphoma-2 (bcl-2) were determined with immunohistochemistry tests.@*RESULTS@#Subcutaneous injection of K562 cells induced tumor formation in nude mice, and the TSRP treated group showed a signifificant inhibitory effect on tumor formation. The nude mice treated with TSRP showed a signifificant decrease in tumor growth rate and tumor weight in comparison to the control group (all P<0.05). The HE staining and TUNEL assay showed that TSRP induced cell death by apoptosis. The immunohistochemical assay showed down-regulation of the bcl-2 gene in the TSRP treated cells. The phosphorylation levels of eIF4E and STAT3 were decreased obviously after the treatment of TSRP.@*CONCLUSION@#TSRP had an excellent tumor-suppressing effect on K562 cells in the nude mice xenograft model, suggesting that TSPR can be developed as a promising anti-chronic myeloide leukemia drug.


Subject(s)
Animals , Apoptosis , Eukaryotic Initiation Factor-4E , Physiology , Humans , K562 Cells , Leukemia , Drug Therapy , Pathology , Male , Mice , Rubus , Chemistry , STAT3 Transcription Factor , Physiology , Saponins , Pharmacology , Signal Transduction , Xenograft Model Antitumor Assays
18.
Article in English | WPRIM | ID: wpr-691359

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells.</p><p><b>METHODS</b>A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flfl anks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m•d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34CD38, CD34CD38CD123, CD34CD38CD96 and CD34CD38CD33, in KG-1a cell line tumor xenografts were detected by flfl ow cytometry.</p><p><b>RESULTS</b>Compared with the control and ADM groups, expression of CD34CD38 in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34CD38CD123 in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34CD38CD96 and CD34CD38CD33 in the two CZG groups decreased (P<0.05).</p><p><b>CONCLUSIONS</b>CZG combined with doxorubicin could reduce the expression of CD34CD38, CD34CD38CD123, CD34CD38CD96 and CD34CD38CD33 in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization.</p>


Subject(s)
Animals , Antigens, Surface , Metabolism , Cell Line, Tumor , Cell Proliferation , Cell Shape , Doxorubicin , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Female , Humans , Mice, Inbred BALB C , Subcutaneous Tissue , Pathology , Xenograft Model Antitumor Assays
19.
Braz. j. med. biol. res ; 51(4): e6803, 2018. graf
Article in English | LILACS | ID: biblio-889059

ABSTRACT

Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.


Subject(s)
Animals , Female , Apoptosis/drug effects , Endometrial Neoplasms/drug therapy , Hypnotics and Sedatives/pharmacology , Propofol/pharmacology , SOXC Transcription Factors/metabolism , beta Catenin/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Endometrial Neoplasms/pathology , Mice, Inbred BALB C , Neoplasm Invasiveness , Propofol/administration & dosage , Tumor Stem Cell Assay , Wnt Proteins/metabolism , Xenograft Model Antitumor Assays
20.
Article in English | WPRIM | ID: wpr-296520

ABSTRACT

<p><b>OBJECTIVE</b>A subcutaneous transplantation tumor model of human HT-29 cells was established in nude mice to study the anticarcinogenic activities and apoptosis-regulatory mechanistic effect of aqueous extract of fermented barley with Lactobacillus plantarum dy-1 (LFBE).</p><p><b>METHODS</b>HT-29 cells were transplanted via subcutaneous injection of 1 × 107cells into the right flank of each nude mouse. Then, nude mice were treated for 30 days with LFBE (high-dose 2 g·kg-1·d-1; low-dose 1 g·kg-1·d-1) and for 7 days with 5-fluorouracil (5-FU, 25 g·kg-1·d-1) by gavage and intraperitoneal injection, respectively.</p><p><b>RESULTS</b>Tumor volume and weight decreased significantly in both groups of nude mice treated with LFBE. In addition, the cell apoptosis rate of the LFBE group was significantly higher than that of the control group and 5-FU groups as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot methods further confirmed these apoptosis-enhancing and growth-inhibiting effects. The involvement of LFBE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and cyclinD1.</p><p><b>CONCLUSION</b>The results showed that LFBE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be used as a natural nutrient supplement or chemopreventive agent in the treatment of human colon cancer.</p>


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Proliferation , Cyclin D1 , Metabolism , Female , Fermentation , HT29 Cells , Hordeum , Chemistry , Humans , Lactobacillus plantarum , Mice, Nude , Neoplasm Transplantation , Neoplasms, Experimental , Drug Therapy , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein , Metabolism
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