Mechanism of Cryptotanshinone Inhibiting Proliferation of Human Breast Cancer MCF7 Cells / 肿瘤防治研究

Objective To investigate the inhibitory effect of cryptotanshinone (CPT) on human breast cancer cell MCF7 and its mechanism. Methods The survival rate of MCF7 cells was measured by MTT assay. Cell apoptosis was detected by Annexin V/PI assay and Hoechst 33258 fluorescence staining assay. Cell cycle and reactive oxygen species were detected by flow cytometry. Cell migration and invasion were detected by cell scratch test and Transwell chamber test. The surface molecules CD44 and CD24 were detected by flow cytometry and microsphere culture. The expression of cell-associated proteins was detected by Western blot. Results CPT inhibited the proliferation of MCF7 cells in a dose-dependent manner, and the 24 h IC50 value was 19.24 μmol/L. Compared with the untreated group, the CPT-treated group showed cell cycle arrested in the S phase, and apoptosis was induced. The results of the cell scratch and Transwell chamber tests showed that CPT significantly inhibited the migration and invasion of MCF7 cells. Furthermore, CPT reduced the CD24-/LowCD44+ cell population in MCF7 cell-derived microspheres. Western blot results showed that CPT could up-regulate the expression of Bax protein, down-regulate the expression of BCL-2, PI3K-p85, Akt, N-cadherin, Twist1, Sox2, Oct4, and Nanog protein, effectively inhibit the phosphorylation of ER-α, and decrease the expression of ABCG2. Conclusion CPT can inhibit the proliferation of MCF7 cells by inhibiting the migration and invasion of MCF7 cells, decreasing the number of CD24-/lowCD44+ cells and affecting the expression of tumor stem cell-related proteins.

Silencing long non-coding RNA HIF1A-AS2 inhibits proliferation, invasion and migration of cervical cancer cells / 南方医科大学学报

OBJECTIVE@#To explore the inhibitory effects of silencing long non-coding RNA (LncRNA) HIF1A-AS2 on epithelialmesenchymal transition (EMT) and tumor stem cell-like phenotype in cervical cancer cells.@*METHODS@#We designed 3 shRNA constructs for silencing HIF1A-AS2 in CaSki cells, and the shRNA with the strongest interference effect was selected for subsequent experiment. CaSki cells were transfected with shRNA-NC or Sh-HIF1A-AS2, and the changes in cell viability, invasion ability, EMT, expressions of EMT-related proteins, formation of cell spheres and expressions of stem cell markers were detected.@*RESULTS@#Transfection with shRNA-NC and Sh-HIF1A-AS2 did not significantly affected the viability of CaSki cells (@*CONCLUSIONS@#Silencing HIF1A-AS2 can inhibit proliferation, invasion and migration of cervical cancer cells

Role of ovarian tumor stem-like cells sorted from human epithelial ovarian cancer SKOV3 cells in vasculogenic mimicry formation / 南方医科大学学报

OBJECTIVE@#To isolate tumor stem-like cells from human epithelial ovarian cancer SKOV3 cells and explore their role in the formation of vascularization mimicry (VM).@*METHODS@#SKOV3 cells were passaged to the 7th generation by suspension culture in serum-free medium, and the percentages of CD133- and CD117-positive cells in the 1st, 3rd, 5th and 7th generations were analyzed using flow cytometry. The proliferative activity of the cells sorted from the 7th generation SKOV3 cells was assessed with colony formation assay. A three-dimensional cell culture model was established to compare the ability of VM formation between the sorted cells and the parental SKOV3 cells. The expression levels of matrix metalloproteinases-2 (MMP-2) and MMP-9 in the two groups were detected using real-time PCR and Western blotting.@*RESULTS@#Some SKOV3 cells formed typical cell spheres with suspension growth in serum-free medium and were passaged to the 7th generation. Flow cytometry revealed that the percentage of CD133-positive cells increased with cell passaging. The cloning efficiency of the sorted cells was significantly higher than that of the parental SKOV3 cells (50.33% 5.33%, < 0.001). The VM formation ability of the sorted cells was stronger than that of the parental SKOV3 cells in the three-dimensional cell culture system. RT-PCR and Western blotting showed that the expression levels of MMP-2 and MMP-9 were significantly higher in the 7th passage cells than in the parental cells ( < 0.05).@*CONCLUSIONS@#The sorted cells from SKOV3 cells cultured in serum-free medium exhibit biological properties of tumor stem cells with strong VM formation ability, suggesting their role in VM formation.

Differentiation of breast cancer stem cells into vascular endothelial cells and tumor angiogenesis / 西安交通大学学报(医学版)

Objective To explore the potential of breast cancer stem cells in differentiating into vascular endothelial cells and participating in the angiogenesis of breast tumor.Methods The expressions of mutant P53, CD31 ,VEGF and Her-2 amplification in tumor blood vessels were detected and the single cell suspension of breast cancer was prepared.CD44+/CD24-/low cells were selected and cultured in culture system.The expressions of CD31 and CD105 on endothelial cell surface were detected by EGM-2 endothelial cell culture medium.The ability of uptake of acetylated low-density lipoprotein was measured.The endothelial cells were cultured in vitro to observe their vascular structure.Results The expressions of CD31,VEGF and mutant P53 were found in paraffin sections of breast cancer tissue samples, and they were arranged along the vessel lumen or blood vessel sphere. Immunofluorescence showed that CD31 and DAPI signals were expressed intravascularly in breast cancer tissues. Four samples of Her-2 positive amplification and 9 cases of non-amplification were detected in the samples.The successful separation of breast cancer stem cells was carried out by immunomagnetic sorting.The percentage of CD44+ cells in the pre-sorting cells was (7.5±2.6)% and that of CD44+ cells was about (94.3±4.7)% after magnetic sorting (P<0.05).The ratio of CD24+ cells was (48.2±9.4)% before sorting,and that of CD24+ cells was (4.3±1.6)% after immunomagnetic bead sorting.The proportion of CD105+ cells in mammary gland cells was (4.5±0.9)% and the proportion of CD31+ cells was (6.2±1.3)%.After cultured for three generations,the percentages of CD105+ cells and CD31+ cells were (79.6±9.3)% and (84.1±10.7)%,respectively (P<0.05). DiL-Ac-LDL could be phagocytized by endothelial cells cultured in endothelial cell culture system.Vessel-like structure was found in the endothelial cell group while the control group did not have the tendency of vascular changes.Conclusion Breast cancer stem cell-derived endothelial cells differentiate into endothelial cells in vitro and have the ability of vascular formation,suggesting that breast cancer stem cells may be involved in the formation of tumor blood vessels.

Effect and its significance of Wnt/β-catenin signaling pathway by controlling tumor marker CD44 on nasopharyngeal carcinoma SP cells / 中国耳鼻咽喉头颈外科

[ABSTRACT]OBJECTIVEThis study aims to explore the molecular mechanism and expression of Wnt/β-catenin signaling pathway and tumor marker CD44 in nasopharyngeal carcinoma cells after transfection withβ-Catenin when the Wnt/β-catenin signaling pathway was blocked.METHODSSP cells and CD44+SP cells isolated from the nasopharyngeal carcinoma cell line CNE-2 by flow cytometry were identified. Changes in the number and biological characteristics of CNE-2 and CD44+SP cells in vitro were investigated after the Wnt/β-catenin signaling pathway was blocked through siRNA.RESULTSSP cells accounted for 2.3% of nasopharyngeal carcinoma CNE-2 cells, andCD44+SP cells accounted for 36.5% of the SP cells. CD44+SP cells showed significantly higher in vitro proliferation and resistance to chemotherapy (P<0.05). After transfection withβ-Catenin siRNA, the proliferation, cloning efficiency, and tolerance to chemotherapeutic drugs of the cells were found statistical differences compared with those before transfection ofβ-Catenin siRNA. CONCLUSIONWnt/β-catenin signaling pathway abnormalities are closely related to the biological behavior of nasopharyngeal carcinomaCD44+SP cells. Interference of this pathway can change the characteristics of nasopharyngeal carcinoma stem cells.

Isolation and tumorigenicity of CD133 + subpopulation in human hepatocellular carcinoma / 中华肝胆外科杂志

Objective To separate the CD133 + subpopulation in human hepatocellular carcinoma (HCC) and investigate the tumorigenicity.Methods The human liver cancer tissues were subcutaneously transplanted into nude mice to generate xenograft tumors which were then isolated to prepare single cell suspension.The expression of CD133 + subpopulation was further detected using flow cytometry.The CD133 + subpopulations were separated and depurated with magnetic-activated cell sorting system.Immunofluorescence was performed to identify the histological phenotype of CD133 + subpopulation.The in vitro and in vivo clone formation assay and in vivo xenograft formation assay were performed, respectively.Results Flow cytometry analysis revealed that a percentage of (4.1 ± 0.6) ％ CD133 + cells were detected in xenografts.Immunofluorescence studies showed that (86.8 ± 7.5) ％ of the isolated cells were CD133 +.Compared with CD133-population, CD133 + cells showed a higher capability to generate clone sphere in vitro and a higher tumorigenicity in nude mice (P ＜ 0.05).Conclusion The CD133 + subpopulation in human hepatocellular carcinoma had a potent tumorigenicity and was enriched in cancer stem cells.

The effect of secreted cytokines from killer cells induced by cytokines on apoptosis of hepatic cancer stem cells / 肿瘤

Objective: To investigate the effect of secreted cytokines from cytokine-induced killer (CIK) cells on apoptosis of human hepatic cancer stem cells (HCSCs). Methods: The HCSCs were enriched from human hepatic cancer cell line HepG2 by serumfree suspension culture and sphere-forming assay. The expressions of CD90 and CD1 33 of HCSCs were examined by flow cytometry (FCM). The tumorigenicity of HCSCs was detected by nude mouse transplantation tumor experiment. The CIK cells were produced from suspended peripheral blood mononuclear cells (PBMCs) induced by interferon γ (IFNγ), CD3 monoclonal antibody and recombinant human interleukin-2 (rhIL-2). The HCSCs were cultured together with CIK cells at different density in a Transwell chamber and cultured separately by the membrane of the Transwell chamber for 24 and 48 h, respectively. The apoptosis of HCSCs, which were cultured with CIK cells for 24 and 48 h, was analyzed by FCM. The expression levels of caspase-3 mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Results: The result of FCM revealed that the stem cell markers CD90 and CD1 33 were highly expressed on the surface of HCSCs. The nude mouse transplantation tumor experiment showed that HCSCs possessed a high ability of tumorigenicity. The apoptosis of HCSCs could be significantly induced by secreted cytokines from CIK cells as compared with that of the control group (P < 0.01). The caspase-3 mRNA and protein expression levels were significantly up-regulated in HCSCs induced by secreted cytokines from CIK cells. Conclusion: The secreted cytokines from CIK cells can induce apoptosis of HCSCs, and this effect may be related to upregulation of caspase-3 expression.

Effects of miR-206/miR-1 on Breast Cancer Stem Cell Proliferation and the Mechanism / 中国医科大学学报

Objective To investigate the effects of up?regulated miR?206/miR?1 on the proliferation of breast cancer stem cells and the effect mech?anism. Methods Breast cancer stem cells(BCSCs)were isolated from breast cancer cell line MCF?7 by fluorescence?activated cell sorting. Cells in the experiment were divided into the blank control group,the negative control group,the miR?206 group and the miR?1 group. The BCSCs were transfected by negative control mimic,hsa?miR?206mimic and hsa?miR?1mimic in all groups except the blank control group. MiR?206and miR?1 expression levels as well as the transcription factor EVI?1 gene were detected by real time PCR. The expression levels of the transcription factor EVI?1 protein were detected by Western blot. MTT method was used to detect the effects of miR?206 and miR?1 on the proliferation of BCSCs. Results The BCSCs(CD44+/CD24-/low cells)isolated from MCF?7 cell lines were successfully cultured in serum?free medium for subsequent studies. After transfection of hsa?miR?206mimic and hsa?miR?1mimic for 48 hours,miR?206and miR?1relative expression levels increased. EVI?1mRNA ex?pression levels significantly decreased. The results of Western blot and MTT showed that up?regulated expression levels of miR?206 and miR?1 could significantly reduce the expression of EVI?1 protein and inhibited the proliferation of BCSCs. The differences in levels of miR?206,miR?1 and EVI?1 protein were statistically significant(P<0.05). Conclusion Up?regulated miR?206 and miR?1 expression can inhibit the proliferation ability of BCSCs,which may be related to the down?regulation of EVI?1.

Células madre y cáncer / Stem cells and cancer

La cirugía, la radioterapia y la quimioterapia siguen siendo los tratamientos reconocidos universalmente como los más efectivos en la lucha contra el cáncer, a pesar de los avances logrados para elucidar sus mecanismos moleculares y haber desarrollado nuevas y sofisticadas técnicas para su tratamiento. Al ser esta enfermedad un importante problema de salud pública, el descubrimiento y estudio de las células madres tumorales ha creado nuevas líneas de investigación dirigidas a comprender y controlar la recurrencia de un tumor, la resistencia a los medicamentos y los mecanismos que hacen posible las metástasis. De esta forma, con una mejor comprensión de las células tumorales, surgen nuevas alternativas terapéuticas que hacen más factible el control y la posible solución que permita la cura definitiva del cáncer. Por la importancia fundamental del tema, el presente artículo tiene como objetivo resumir las características y propiedades de las células madres tumorales, las investigaciones en curso y las nuevas estrategias para la prevención y control de los mecanismos que llevan a la recurrencia de los tumores en los pacientes de cáncer que han sido tratados.

Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence.

The study of microRNA-34 a loaded liposome inhibit lung cancer stem cells / 中国生化药物杂志

Objective To preparemicroRNA-34 a loaded liposome and evaluate the targeting efficiency for lung cancer stem cells and effect on the treatment of lung cancer. Method The liposomes were prepared by thin film hydration method. The particle size,Zeta potential and entrapment efficiency were evaluated. Stability of liposome in serum was evaluated. The efficiency of cellular uptake on lung cancer stem cells in vitro was evaluated. The anti-proliferation efficiency of miLPs-34 a was evaluated by MTT assay. Tumor spheroids were used to evaluate anti-tumor ability of miLPs-34 a. Lung cancer stem cells were used to build orthotopictumor model, which were used to evaluate the effect of anti-cancer. Results The particle diameter of the miLPs-34 a was (136.55±11.4) nm with the Zeta potential of (21.45±4.55) mV. The entrapment efficiency of microRNA-34 awas 94.6%.the results demonstrated that the liposomes could keep stable in 50%serum for 24 h. miLPs-34 a uptaken by lung cancer stem cells were 3.1 times higher than that of microRNA-34 a(P<0.01). The MTT assay confirmed strong inhibitory effect of miLPs-34 a than microRNA-34 a(P<0.01). the inhibition of tumor spheroid confirmed strong inhibitory effect of miLPs-34 a than microRNA-34 a(P<0.01). The anti-tumor of miLPs-34 a was much more effectively than microRNA-34 a(P<0.01).Conclusion the microRNA-34 a loaded liposome could target to lung cancer stem cells and inhibit the proliferation of lung cancer stem cell. MiLPs-34 a, as a new nanometer drug, has a special application value for the therapy of lung cancer stem cell.

Expression of tumor stem cell marker ALDH1 in invasive bladder cancer tissue and its relationship with clinicopathological parameters and prognosis / 吉林大学学报(医学版)

Objective To study the expression of tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1)in invasive bladder cancer tissue and to clarify its relationship with the biological behavior of bladder cancer. Methods The ALDH1 expression in 109 cases of primary invasive carcinomas specimens (case group)and 20 cases of normal bladder tissue surrounding cancer (control group)was detected by immunohistochemistry. At the same time,the ALDH1 expression in 6 cases of metastatic pelvic lymph node tissue and 20 cases of non-metastatic pelvic lymph node tissue was detected. The relationship between the ALDH1 expression and the chinicopathological charateristics of invasive bladder cancer and its influence in the survival rate and disease-free survival were analyzed. Results The positive rates of ALDH1 expression in bladder cancer tissue and normal bladder tissue were 33.94%(37/109)and 5.00% (1/20),respectively,there was significant different between them (P<0.01);they were 19.05% (8/42)and 43.28% (29/67)in the cases with non muscle invasive and nmuscle invasive bladder cancer, respectively,there was significant difference (P<0.01);they were 13.04% (3/23)and 39.53% (34/86)in the cases of bladder cancer with low grade and high grade,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 12.90% (4/31)in the tissue of bladder cancer with metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 0.00%(0/20)in the metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.01).The overall survival rate in the patients with positive ALDH1 expression was 64.9% while it was 84.7% in negative ones,there was significant difference (P<0.05);the disease-free Survival was 51.4% and 75% in the patients with positive and negative ALDH1 groups,respectively,there was significant difference (P<0.05). Conclusion The high expression of tumor stem cell marker ALDH1 is associated with staging, grading and prognosis of invasive bladder cancer.ALDH1 may play a role in the tumorigenesis,progression and metastasis of bladder cancer.

Molecular Culprits Generating Brain Tumor Stem Cells

Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes.

Expressions of CD90 and hTERT in hepatocellular carcinoma and Their Clinical Significance / 中华肝胆外科杂志

ObjectiveTo study the expressions of CD90 and hTERT in hepatocellular carcinoma (HCC),and their relationships to progression of tumor.MethodsThe expressions of CD90 and hTERT in hepatocellular carcinoma were detected by S-P immunohistochemical staining.Twenty patients with hemangiomas of liver were used as control.ResultsCompared with the control group,the positive rates of CD90 and hTERT in HCC were significantly higher (63.9％ and 47.2％ vs 0％ and 0％).The positive rates of CD90 and hTERT were significantly higher in patients with tumors at UICC Ⅲ-Ⅳ stage than at UICC stage Ⅰ -Ⅱ (79.1％ and 62.5％ vs 33.3％ and 16.6％).The CD90 expression correlated with hTERT positively.There were significant differences in survival between patients with CD90+ and CD90- or hTERT+ and hTERT-.The median postoperative survivals for patients with CD90+ and hTERT+,CD90- and hTERT- were 85 d and 76 d,505 d and 463 d,respectively.ConclusionsCD90 expression correlated positively with progression of HCC.It has the potential to serve as a prognostic marker for HCC.

Preparation of a toxicity fusion protein targeting to CD123 on leukemia stem cell / 白血病·淋巴瘤

Objective To construct a fusion protein that used for treatment of resistance and palindromia in leukemia and studied its biological activity. Methods IL-3 and LP gene fragments were amplified by PCR. After enzymatic digestion and T4 ligation, the fusion gene was cloned into expression vector pAYZ. The product was purified by exchange chromatography and anti-Etag affinity chromatography. IL3-G4SLP fusion protein was analyzed by SDS-PAGE and Western blot. Protein biological activity was detected by FACS. Results The fusion protein was expressed as soluble protein by E.Coli 16C9. The protein expression level was about 1 mg/L, its purity was over 95 %, and the expression level was about 1 mg/L. The fusion protein can combined specificely with CD123 on leukemia stem cells. Conclusion Fusion protein IL-3-G4S-LP can target on leukemia stem cells and maybe as a potential drug used for treatment of resistance and palindromia in leukemia.

Experimental research of immunophenotype CD133,CD34,CD44 in human lung adenocarcinoma / 中国医师杂志

Objective To validate the possibility of CD133 CD34 CD44 be served as biomarkers in cancer stem cell of human lung adenocarcinoma. Methods Two kinds of culturing methods were performed to generate adhesive tumor cells and floating aggregates, and the differences of expression of CD133 CD34 CD44 between 2 kinds of cultured cells were observed by immunofluorescence. Results Floating aggregates grew more slowly, kept activity for longer period than adhesive cells (72.5% vs 47.5%,P＜0.05). Floating aggregates expressed higher level of CD133, CD34 and CD44 than adhesive cells (68.97%,82.76%,93.10% vs 5.26%,15.79%,5.26%,P＜0.01). Conclusions The combination of CD133, CD34 and CD44 probably can be used as surface markers of cancer stem cells for human lung adenocarcinoma.

Notch signal pathway and tumor / 第二军医大学学报

Notch signal pathway has extensive influence on the growth and development of cells through modulating cell differentiation, proliferation and apoptosis. It also interacts with the key pathways of tumor formation and progression. Its relationship with tumor is initially established through T cell leukemia induced by mismatch or chromosome translocation. Increasing evidence showed that Notch pathway is associated with the formation and progression of the other types of tumor, such as skin cancer, liver cancer, brain tumors and breast cancers. Notch signal pathway has promoting effect on some tumors (such as brain tumors and breast cancer) and inhibitory effect on others (such as skin cancer and liver cancer). Close relationship was found between Notch pathway and tumor stem cells. Moreover, it may have different functions for different subtypes and different stages of one tumor.

Brain Tumor Stem Cells as Therapeutic Targets in Models of Glioma

At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.

Expression of Oct4 and Wnt2 in human glioma tissues and its clinical significance / 中国肿瘤生物治疗杂志

Objective:To investigate the expression of Oct4 and Wnt2 in human glioma tissues and its relationship with the clinicopathological features of glioma. Methods: Fifty-six paraffin blocks were obtained from glioma patients receiving surgery. The diagnosis of these patients were confirmed by pathology in our hospital from 2006-2009. Immunohistochemi-cal staining was used to examine Oct4 and Wnt2 expression in the brain tissues of 10 patients with acute brain injury and 56 glioma tissues (including 15 recurrent cases). Results: The normal brain tissues were negative of Oct4, with only one case showing weak Wnt2 expression. Thirty-four of the 56 glioma tissues showed positive expression of Oct4 (60.7%), and 40 showed positive expression of Wnt2 (71.4%). Positive expression rates of Oct4 and Wnt2 in low-grade and high-grade glioma tissues were 46.2 %, 73.3% and 57.7 %, 83.3%, respectively (P < 0.05). Oct4 positive rates in the recrudescence and newly diagnosed glioma tissues were 86.7% and 51.2%, respectively (P < 0.05). Oct4 expression in the glioma tissues was positively correlated with that of Wnt2 (r = 0.537, P < 0.01). Conclusion: Expression of Oct4 and Wnt2 is associated with the malignant degrees of glioma, and Oct4 expression is related to the recurrence of glioma. Oct4 might participate in the development and progression of brain glioma through Wnt signaling pathway.

Drug resistance and expression of drug-resistance enzymes in brain cancer stem cells isolated from U251 cell lines / 中国癌症杂志

Background and purpose: Cancer stem cells (CSCs) isolated from human glioma are cancer-initiating cells and sources of tumor recurrence in brain tumors. The poor outcome of glioma is because cancer stem cells can not be eradicated. This article was aimed to explore the resistance of CSCs to chemotherapeutic agents and expression of drug-resistance enzymes in glioma cancer stem cells. Methods: Cancer stem cells from U251 were isolated by using magnetic sorting. The proliferation inhibitory effects of Vumon-26 (Vm-26), bischloronitrosourea (BCNU) and diamminedichloroplatinum (DDP) on U251-CSC and U251 were examined by drug sensitivity testing in vitro (MTT assay) and the apoptosis rates were observed by flow cytometry. Western blot was performed to examine the expression of three drug-resistance enzymes including LRP, MGMT and Topo Ⅱα. Results: Chemotherapeutic agents had a more obvious inhibitory effect on U251 than U251-CSC, as well as higher apoptosis rates. LRP, MGMT and Topo Ⅱα expression were significantly higher in U251-CSC as compared to U251, Conclusion: Glioma stem cells showed strong capability of tumor's resistance to chemotherapeutic agents including Vm-26, BCNU and DDP. This resistance is probably contributed by the CD133 positive cell with higher expression of on LRP, MGMT and Topo Ⅱα.

Advances in the study of tumor stem cells / 基础医学与临床

Nowadays,the study of tumor stem cells has become the heatpoint in cancer research.Many experiments have successfully demonstrated the existence of tumor stem cells,which have been isolated from some solid tumors.As the research on the origin of tumor stem cell is developing,the knowledge of the occurrence and development of tumor has become more clear,which will influence the diagnosis and treatment for tumor significantly.Moreover it will bring benefit to the following-up after surgical operation and giving hopes to cancer sufferers.