Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro

ObjectiveTo address how genistein sensitizes the chemotherapy-resistant ovarian carcinoma cells and promotes apoptosis in the respect of cell cycle and the regulation of survivin expression in the process.MethodsOvarian SKOV-3 carcinoma cell line was treated with genistein or cisplatin either alone or in combination. Cell viability was showed by MTT method. Cell cycle and apoptosis were detected by flow cytometry. Survivin mRNA and protein were revealed by RT-PCR and immunocytochemistry, respectively.ResultsGenistein could reduce the cell viability in a dose-dependent manner, while cisplatin did so at a much higher level. In contrast, if the two agents were treated in combination, half growth inhibition (IC50) value for cisplatin was reduced remarkably and the effect was synergistic as analyzed by isobologram. In particular, the reduced cell viability was exhibited by a switch in cell cycle progression, as the cells were arrested in G2/M phase and the G0/G1 phase-fraction was significantly decreased. The reduced cell viability appeared to involve apoptosis, based on our results from flow cytometry and Hoechst 33258 staining. In the meanwhile, genistein performed the inhibitory effect on cisplatin-induced survivin expression.ConclusionGenistein can sensitize ovarian carcinoma cells to cisplatin therapy with the inhibition of survivin expression as the potential mechanism.