Molecular Mechanism of Apoptosis in Cisplatin-resistant Human Ovarian Cancer Cell Line Promoted by Topotecan

Objective To investigate the cytotoxicity and proapoptotic activity of topotecan(TPT) on cisplatin-resistant human ovarian cancer cell lines COC1/DDP and its mocular mechanisms.Methods The cytotoxicity of TPT on COC1/DDP was monitered using MTT assay and soft agaragar assay. TUNEL and flow cytometry were employed to observe the apoptosis of COC1/DDP induced by topotecan. Western blot were used to determine the expression of bcl-2, bax and caspase-3, in addition to the activity of caspase-3.Results TPT had strong cytotoxicity on COC1/DDP cell in vitro, and the cytotoxicity was dose-and time-dependent. TPT-treated cells demonstrated apoptosis property while the apoptotic rate was increased from 8.54% to 23.16% ( P 0.05 ). Although the expression of bcl-2 was not affected, the expression of bax and caspase-3 were upregulated and the caspase-3 activity was promoted in the course of COC1/DDP apoptosis when treated with topotecan. Conclusion The cytotoxicity and proapoptosis activity of TPT, which is significantly observed in cisplatin- resistant human ovarian cancer, may be related to the increased bax expression and the promoted caspase-3 activity.