| Malignant tumor is one of the mainly hazard for health of human. Owing to Ihe development of therapies in cardiovascular disease, cancer is now rising to the number one killing disease in some countries. The therapy for cancer is a comprehensive method including surgery, chemotherapy, radiotherapy, biological therapy, immunotherapy and so on. But surgery and radiotherapy are only suitable for the patients in early stage of cancer. On the other hand, cancer is a systemic disease and many patients are already in late stage at the time of diagnosis and they would be in relapse or metastasis even with effective treatment. So chemotherapy and biological therapy are becoming more important in the treatment of cancer. Over the last 3~5 decades, chemotherapy has relied primarily on the use of various forms of cytotoxic drugs. Although the routine chemotherapy really can get some remission rates, patients always can not tolerance k due to the severe toxic and side effects. And in the long-period treatment procedure, patients could get resistance to some chemotherapy drugs and lead to the failure of chemotherapy or relapse of tumor.In recent years, many new chemotherapy drugs were being used in clinic with the further study of mechanism of tumor occurrence, but there still have many problems need to be solved. Despite the traditional toxic drugs, a lot of new anti-cancer drugsaiming directly to the multiple targets for cancer therapy have been developed, especially the telomerase inhibitors, drug-resistance reversal medicines, differentiation inducers and apoptosis inducers. At the same time, seeking of effective and active components from nature products is a new strategy for the development of anti-cancer agents.Sophora Flavescenes Ait is a widely used traditional Chinese medicine and has diverse biological activities including anti-inflammation, anti-virus, anti-cardiac arrhythmia, and so on. Based on its traditional research before, the anti-cancer property of Sophora Flavescenes Ait had been paid more attention in vitro. The inhibition effects on some tumor model of mouse such as sarcoma S180, lymphocytic leukemia LI 210 and melanoma had been demonstrated. Matrine (chemical formula is CisFb^O with molecular weight of 248.37 D), as its mainly alkaloid component, might also have anti-tumor effects. The clinical using of matrine in leukopenia or cardiac arrhythmia exhibited no significant toxic or side effects, which may have important potential clinical value.Using of transplantated neoplasm in experimental animals was a major method to search for compounds as anti-cancer agents before, but with the developing and popularit of tissue culture technique, it becomes the first important selective way to search new agents through cancer cell lines cultured in vitro. K562, a human erythroleukemia cell line, was widely used. K562/Vln and K562/Dox were two MDR cell lines established in our institute which had typical mdrl gene expression and P-gp overexpression, the resistant factors of them to many anti-cancer agents were 10 to more than 3000 folds.In this study, we chose K562 and its MDR variants to investigate the cell biological effects of matrine on different aspects such as telomerase inhibition, apoptosis inducing and drug-resistance reversal. The objective is to confirm the anti-tumoractivity of matrine and to explore its potential targets and mechanisms.PartLProliferative and telomerase inhibition effects of matrine on K562 cellsNo-restricted rapid proliferation is a character of malignant tumor cells. The immortalization of cancer cells is the key point of tumor growth or metastasis, while telomerase plays important role in immortalization. In this part, MTT assay was applied to evaluate the proliferative inhibition effects of matrine on K562 cells. TRAP-PCR-silver staining and ELISA methods were used to detect the telomerase activity and RT-PCR assay was applied to detect hTERT-mRNA expression. The results showed that matrine exhibited dose-dependent proliferative inhibition effect a... |
PDF Full Text Request