Nedaplatin Induced Apoptosis in Human Ovarian Cancer Cisplatin-resistant Cell Lines in vitro and Investigated Its Mechanism

Objective To study inhibition of nedaplatin(NDP) on human ovarian cancer cell lines SKOV3 with intrinsic cisplatin-resistance and SKOV3/DDP with acquired cisplatin-resistance and investigate its mechanism. Methods MTT assay was used to evaluate the inhibition in different concentration and time of NDP treatment on SKOV3 and SKOV3/DDP cells,then calculated inhibitory concentration(IC50).Cell apoptosis and cycle were detected by flow cytometry (FCM).The changes of Bcl-2,Bax,caspase-3,caspase-9,MMP-2 in mRNA levels were quantified by RT-PCR. Results NDP inhibited the growth of SKOV3 and SKOV3/DDP cells significantly in time and dose-dependent manner.The result from FCM showed that apoptotic rate and the percentage of S-phase cells tend to increase in time and concentration of nedaplatin dependent manner(P<0.05).Compared with control groups,there were a decrease in Bcl-2 and MMP-2 mRNA expression,but an increase in Bax,caspase-3 and caspase-9. Conclusion NDP can inhibit proliferation of SKOV3 and SKOV3/DDP cells.The effect may be ascribed to inducing cell apoptosis，the S-phase arrest and the down-regulation of Bcl-2,MMP-2 expression,up-regulation of Bax,caspase-3 and caspase-9 expression.NDP can suppress MMP-2 expression,so it maybe can reduce invasion force of ovarian cancer.