Study of the anti-tumoral effect by TSDH in humanbreast adenocarcinoma cells

• Main Authors: Chun-I Wang, 王俊懿
• Other Authors: Yu-Chih Liang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/28531340007210685052

碩士 === 臺北醫學大學 === 醫學技術學系 === 94 === Epidemiological studies have indicated that breast cancer is one of the　leading cancer of death for women in Taiwan. At patient, surgical therapy and chemotherapy are the major strategies for the cure of breast cancer. The chemotherapeutic drugs are usually designed to induce cancer cell death via cell cycle arrest and/or apoptosis pathways. In this study, we used a chemical drug-TSDH to inhibit breast cancer cell proliferation and tumor growth, and investigate the underlying molecular mechanisms. Both human breast cancer cell lines-MCF-7 and MDA-MB-231 are used in this study, and found TSDH significantly decreased cell proliferation by a dose-dependent manner in both cells. Flow cytometry demonstrated that TSDH induced cell cycle arrest at G0/G1 phase in synchronous MCF-7 and MDA-MB-231 cells. When analysis the expression of cell cycle-related proteins, we found that TSDH reduced cyclin D, cyclin E and CDK4 expression, and increased CDK inhibitor p27Kip1 in a dose-dependent manner. In addition, TSDH inhibited the activities of CDK2 and CDK4 by a immunocomplex kinase assay. On the other hand, TSDH also induced apoptosis in both cells, In TSDH treatment cells, the anti-apoptotic protein Bcl-xL was decreased and cytochrome c released into cytoplasm was increased. Moreover, TSDH activated caspase-9, caspase-3 and caspase-7 and resulted in PARP cleavage and cell apoptosis. In nude mice experiment, 10 mg/kg TSDH significantly inhibited the tumor growth of MDA-MB-231 cells, Taken together, these results suggest that TSDH could inhibit human breast cancer cell proliferation and tumor growth, and might be a potential drug for chemothera.