The reversible effect of medroxyprogesterone acetate on drug resistance of human ovarian carcinoma cell line SKOV3/DDP to cisplatin

Objective:To reverse the drug resistance of human ovarian carcinoma cell line SKOV3/DDP to cisplatin by medroxyprogesterone acetate(MPA) in vitro,and explore the mechanism preliminarily. Methods:MTT method was used to detect the cytotoxicity of MPA to SKOV3/DDP cells,the non-cytotoxic dose was selected as reversible dose,the change of drug resistance of SKOV3/DDP to cisplatin was detected after treated with MPA of non-cytotoxic dose combined with cisplatin,flow cytometry was used to detect cell cycle and apoptosis. Results:When the concentration of MPA was higher than 7.50 g/L,MPA inhibited SKOV3/DDP cells of varying degrees,showing a dose-dependent manner.When the concentration of MPA was lower than 15.85g/L,MPA had no apparent inhibiting effect on cell growth(cell survival rate90%),thus,15.00 g/L was selected as reversible dose.After treating SKOV3/DDP cells by cisplatin combined with MPA(15.00 g/L) for 24,48 and 72 hours,the IC50 values of cisplatin decreased to(57.72±0.48) g/L,(13.39±0.21) g/L and(7.93±0.18) g/L,respectively;the reversal multiples were 1.22,1.90 and 2.44,respectively.The cell cycle of SKOV3/DDP cells was arrested at G0/G1 phase after treated with cisplatin combined with MPA,the proportion of SKOV3/DDP cells at S phase decreased,and the apoptosis rate increased. Conclusion:MPA can reverse the drug resistance of ovarian carcinoma to cisplatin,the possible mechanism is MPA can promote cell apoptosis and arrest the course of cell cycle.