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1.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 17-25, 2024.
Article in Chinese | WPRIM | ID: wpr-1012688

ABSTRACT

ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action. MethodOn the basis of preliminary research, the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines, and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species (ROS) and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 (p53), Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 and 9 (Caspase-3 and Caspase-9) proteins in A549 cells. ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen, with 50% inhibitory concentration (IC50) being (86.83±2.88) mg·L-1 and (95.10±18.13) mg·L-1, respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC50 value was (4.71±0.81) mg·L-1. The IC50 values of the 40%, 60%, and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were (45.32±4.38)、 (14.95±0.73)、 (17.07±1.76)、 (14.46±2.35)、 (51.7±2.26)、 (12.37±0.67)、 (20.29±0.93)、 and (3.43±0.91) mg·L-1, respectively. Compared with the normal group, the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis (P<0.01). Compared with the normal group, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax (P<0.01). Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 (P<0.01). ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium, which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells, promoting their apoptosis, increasing the expressions of apoptotic proteins such as p53 and Bax, and reducing the expressions of Caspase-3 and Caspase-9.

2.
Journal of Zhejiang University. Medical sciences ; (6): 1-14, 2024.
Article in English | WPRIM | ID: wpr-1009949

ABSTRACT

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

3.
Braz. j. med. biol. res ; 56: e12638, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1447691

ABSTRACT

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

4.
Acta Pharmaceutica Sinica ; (12): 3539-3548, 2023.
Article in Chinese | WPRIM | ID: wpr-1004637

ABSTRACT

Cancer and cardiovascular diseases are the two major causes of death worldwide. The application of anti-tumor drugs has significantly improved the prognosis of patients, the cardiovascular toxicity caused by the application of them has become an important factor affecting the survival and prognosis of cancer patients. Therefore, the prevention and treatment of cardiovascular toxicity related to cancer treatment is increasingly important. The cardiovascular toxicity associated with anti-tumor drugs exhibits different clinical manifestations and involves multiple pathological mechanisms. This article reviews the current research progress from the perspective of the characteristics, molecular mechanisms and prevention and treatment strategies of cardiovascular toxicity caused by cancer drugs.

5.
Cancer Research on Prevention and Treatment ; (12): 1180-1184, 2023.
Article in Chinese | WPRIM | ID: wpr-1003797

ABSTRACT

Cholangiocarcinoma is a bile duct adenocarcinoma derived from the bile duct epithelium. Current treatment strategies for cholangiocarcinoma include surgery, chemotherapy, and radiotherapy. Surgical treatment is the first choice for all subtypes of cholangiocarcinoma. However, cholangiocarcinoma has the characteristics of high malignancy, easy recurrence after surgery, and low 5-year survival rates. Recent studies have found that many traditional Chinese medicines exhibit excellent anti-tumor effects in the treatment of various cancers, including cholangiocarcinoma. These medicines have advantages, such as low prices and abundant reserves, and are considered as an effective and safe complementary and alternative therapy for the treatment of cholangiocarcinoma. This article aims to review the effects of traditional Chinese medicine on cholangiocarcinoma from different aspects and levels in recent years. Results will provide new ideas for the prevention and treatment of cholangiocarcinoma.

6.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 1098-1105, 2023.
Article in Chinese | WPRIM | ID: wpr-1015634

ABSTRACT

CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.

7.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 880-888, 2023.
Article in Chinese | WPRIM | ID: wpr-1015623

ABSTRACT

Tumor cells can use different strategies to suppress the immune system and disable them for killing tumor cells. Previous studies have shown that recombinant human peroxiredoxin-5 (hPRDX5) can activate the normal anti-tumor immune, so as to control and eliminate the tumor cells, but its exact mechanism of action needs to be studied in depth. The study aimed to investigate whether hPRDX5 exerts its anti-tumor activity by activating or reversing the polarization state of mouse macrophages RAW264. 7 cells. The results of CCK8 showed that different doses of hPRDX5 could significantly enhance the viability of macrophage compared with the control group (P < 0. 001); The results of Nitric oxide (NO) test showed that hPRDX5 significantly enhanced NO secretion levels in RAW264. 7 cells (P < 0. 001); ELISA experiments revealed that hPRDX5 promotes TNF-α (P<0. 01) and IL-6 (P<0. 001) secretion in RAW264. 7 cells; Flow cytometry revealed that hPRDX5 increased the expression of antigen differentiation cluster (CD) 80 (P < 0. 01) and inducible nitric oxide oxide synthase (iNOS) (P < 0. 001) in RAW264. 7 cells, and reduced the expression of CD206 (P < 0. 001) in RAW264. 7 cells induced by tumor conditional culture solution (TCS); Lactate dehydrogenase (LDH) experiments revealed that hPRDX5 can increase the killing activity of mouse macrophages on mouse pancreatic cancer Panc02 cells. hPRDX5 is able to activate mouse macrophage RAW264. 7 cells, promotes its M1-type polarization, reverses M2-type polarization, and exerts antitumor activity through the immune-enhancing effect.

8.
Acta Pharmaceutica Sinica B ; (6): 4305-4317, 2023.
Article in English | WPRIM | ID: wpr-1011164

ABSTRACT

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.

9.
Journal of Central South University(Medical Sciences) ; (12): 1128-1135, 2023.
Article in English | WPRIM | ID: wpr-1010336

ABSTRACT

OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.


Subject(s)
Humans , Nasopharyngeal Carcinoma , Paclitaxel/therapeutic use , Nasopharyngeal Neoplasms/metabolism , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Proliferation , Cell Line, Tumor
10.
Acta Pharmaceutica Sinica B ; (6): 2613-2627, 2023.
Article in English | WPRIM | ID: wpr-982865

ABSTRACT

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

11.
Acta Pharmaceutica Sinica B ; (6): 1554-1567, 2023.
Article in English | WPRIM | ID: wpr-982823

ABSTRACT

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

12.
Chinese Herbal Medicines ; (4): 169-180, 2023.
Article in English | WPRIM | ID: wpr-982507

ABSTRACT

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

13.
Journal of Pharmaceutical Practice ; (6): 207-211, 2023.
Article in Chinese | WPRIM | ID: wpr-972313

ABSTRACT

Cryptotanshinone is one of the effective components of traditional Chinese medicine salvia miltiorrhiza which shows good activities against a variety of tumors. Its anti-tumor effects include inhibition of tumor cell proliferation, induction of cell apoptosis, inhibition of cell migration and invasion, regulation of immune function and reversal of drug resistance. The direct anti-tumor targets include signal transducer and activator of transcription 3 (STAT3), tyrosine protein phosphatase SHP2, DNA topoisomerase 2, and other mechanisms of action include the induction of reactive oxygen species (ROS) production, regulation of estrogen and androgen receptor signaling, and inhibition of PI3K/AKT signaling pathway. In addition, many cryptotanshinone derivatives have been designed and synthesized to study the antitumor effects. The research progress of the antitumor activity of cryptotanshinone and its derivatives were reviewed in this paper to give references to the anti-tumor drug development of cryptotanshinone and its derivatives.

14.
China Pharmacy ; (12): 1014-1019, 2023.
Article in Chinese | WPRIM | ID: wpr-972278

ABSTRACT

Hedgehog (Hh) signaling pathway plays an important regulatory role in the process of cell proliferation, differentiation and tissue formation. Proper intensity and action time of Hh signal are crucial for the normal development of various tissues of the body, and its abnormal activation will lead to the occurrence and development of most malignant tumors, including breast cancer, liver cancer, pancreatic cancer, and lung cancer, which makes Hh signaling pathway an ideal target for anti-tumor drug research and development. At present, the main targets of Hh signaling pathway inhibitors include Hh ligand, receptor Smoothened (Smo) and transcription factor Gli. Among them, the compounds that depend on the Hh ligand pathway still remain at the stage of laboratory research because they cannot act on the non-classical Hh signaling pathway. The special structure of Smo protein enables it to combine with drugs efficiently and selectively, which is a powerful and effective drug target. Therefore, Smo selective inhibitors have been an active field of related research, and many Smo inhibitors have entered the clinical use or trial stage. Gli can regulate multiple carcinogenic genes, promote abnormal cell proliferation and lead to tumor, and can also cause feedback inhibition to Hh signaling pathway. Therefore, the development of drugs that can inhibit the activity of Gli has broad prospects. In the future, a combination of multiple pathway inhibitors can be designed to avoid drug resistance and other side effects.

15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 246-253, 2023.
Article in Chinese | WPRIM | ID: wpr-961705

ABSTRACT

In China, malignant tumors have become the main cause of death. In the past half century, the incidence and mortality of malignant tumors have been on the rise, posing a threat to health of patients, and the burden of cancer has been increasing. At the moment, malignant tumors are mainly treated by surgery, radiotherapy, and cytotoxic drugs, which, however, have limitations and induce great adverse reactions. As biological technology and the research on tumor microenvironment, immunology, cell biology, and molecular biology advance, high-efficiency low-toxicity targeted therapy has attracted wide attention in the treatment of tumors. Epidermal growth factor receptor (EGFR) plays an important role in many cellular processes such as cell proliferation, survival, differentiation, migration, inflammation, and stromal homeostasis. EGFR promotes tumor growth, proliferation, and metastasis in a variety of ways. Chinese medicine has unique efficacy in the comprehensive treatment of malignant tumors. Through multiple components, multiple targets, and multiple pathways, it enhances the efficacy, reduces toxicity, prolongs life, and improves life quality in the treatment of tumors. Many Chinese medicines and their active components exert anti-tumor effect by inhibiting the EGFR signal transduction pathway. Through targeted inhibition of EGFR, Chinese medicine can promote the apoptosis and autophagy of tumor cells, suppress the proliferation and metastasis of tumor cells, and delay the progression of tumors. Thus, EGFR is a potential target for suppressing tumor. This paper summarizes the relationship between EGFR signal transduction pathway and tumor occurrence and development and analyzes the anti-tumor action mode and possible mechanisms of Chinese medicine and the active components by regulating EGFR signaling pathway, which is expected to provide a reference for clinical practice.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 264-271, 2023.
Article in Chinese | WPRIM | ID: wpr-960931

ABSTRACT

Digestive tract diseases, especially digestive tract tumors, including liver cancer, pancreatic cancer, and colorectal cancer, have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world, and the incidence and mortality of tumor diseases have been increasing year by year. Therefore, the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology, more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor, immunomodulatory, cardiac boosting, pain-easing, anti-inflammatory, and swelling-relieving activities. In clinical practice, cinobufotalin is mainly used to assist the treatment of liver cancer, lung cancer, colorectal cancer, gastric cancer and other malignant tumors, which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis, regulating cell cycle, inhibiting cell proliferation and angiogenesis, modulating immune response, reversing multidrug resistance, enhancing radiochemotherapy sensitivity, inhibiting tumor inflammation, invasion, and metastasis, etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years, aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin, promote the application of cinobufotalin in tumor treatment, and facilitate the further research and development of this compound.

17.
Journal of Southern Medical University ; (12): 906-914, 2023.
Article in Chinese | WPRIM | ID: wpr-987003

ABSTRACT

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.


Subject(s)
Animals , Humans , Mice , Apoptosis , Dendritic Cells/immunology , Glycyrrhizic Acid/pharmacology , HMGB1 Protein , Lung Neoplasms/immunology
18.
Journal of Pharmaceutical Practice ; (6): 465-471, 2023.
Article in Chinese | WPRIM | ID: wpr-984554

ABSTRACT

Bavachinin is a dihydroflavone isolated from dried ripe fruits of Psoralea corylifolia L.,which has various pharmacological activities, such as anti-tumor, anti-virus, anti-diabetes, anti-inflammatory and neuroprotective, and good potential in clinical applications. With the increasing concern about the safety of P. corylifolia applications in clinical, the bavachinin has been found to be one of the main components causing liver injury. In this paper, the pharmacological activities and hepatotoxicity of bavachinin in the recent 20 years were reviewed, in order to provide reference for the further study and clinical application.

19.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 264-272, 2023.
Article in Chinese | WPRIM | ID: wpr-973769

ABSTRACT

Malignant tumors, with the increasing crude morbidity and mortality year by year, have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions, which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth, improve the quality of life of patients, and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years, they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis, inhibition of tumor cell migration and invasion, suppression of proliferation, induction of autophagy of tumor cells, cell cycle arrest, inhibition of tumor angiogenesis, regulation of microRNA, and modulation of immunity. In addition, Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), mammalian target of rapamycin (mTOR), Notch, Hedgehog, Wnt/β-catenin, and other signaling pathways to participate in the processes of tumor proliferation, invasion and metastasis, autophagy and apoptosis, and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility, utilization, and anti-tumor activity of alkaloids, bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids, their representative derivatives, and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.

20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 274-282, 2023.
Article in Chinese | WPRIM | ID: wpr-973158

ABSTRACT

Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore, the search for new, safe, and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus, with anti-inflammatory, anti-malarial, anti-parasitic, and other pharmacological activities, and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation, apoptosis, invasion, and migration of lung cancer, liver cancer, pancreatic cancer, intestinal cancer, and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs, thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant, the specific antitumor molecular mechanism of bruceine D is still unclear, and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore, based on the research on bruceine D in China and abroad in recent years, this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects, namely, tumor cell proliferation, apoptosis, metastasis and invasion, glucose metabolism process, autophagy, and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.

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