Molecular mechanism of apoptosis in cisplatin-resistant human ovarian cancer cell lines promoted by topotecan

Objective To investigate the cytotoxicity and apoptotic activity of topotecan(TPT) on cisplatin-resistant human ovarian cancer cell lines A2780/DDP and COC1/DDP.Methods The cytotoxicity of TPT on A2780/DDP and COC1/DDP were monitored by MTT assay.TPT-induced apoptosis was determined by DNA ladder and transmission electron microscope(TEM).Western blot was employed to observe the expression of bcl-2 and bax. Results TPT had strong cytotoxicity on A2780/DDP and COC1/DDP cells in vitro and the drug IC 50 were 102.91ng/ml and 111.75ng/ml, respectively.TPT-treated cells demonstrated apoptosis property such as typical DNA ladder,nuclear chromatin pycnosis and margination,cell shrinkage, and cytoplasm condensation.Western blot showed that bcl-2 expression was not fluctuated,but the level of bax expression was upregulated with a dose-dependent pattern,The bax/bcl-2 ratio went up when TPT dose increased over 50ng/ml. Conclusion The cytotoxicity and proapoptosis activity of TPT, is significantly observed in cisplatin- resistant human ovarian cancer,cell line may be related to high expression of bax and the increasing of bax/bcl -2.