[Effects of mifepristone on the proliferation, apoptosis, and cis-platinum (DDP) sensitivity of chemo-resistant human ovarian cancer cells].

BACKGROUND & OBJECTIVE: Mifepristone is an effective progesterone receptor antagonist. It was reported that mifepristone can inhibit the growth of ovarian carcinoma cells either in vitro or in vivo, but the exact mechanism is unknown. The effect of mifepristone on the growth, apoptosis and cis-platinum (DDP)-sensitivity of chemo-resistant ovarian carcinoma cell lines have scarcely been reported. The purpose of this study was to investigate the effect and its mechanism of mifepristone on the proliferation, apoptosis and DDP sensitivity of DDP-resistant human ovarian carcinoma cells, and to give experimental basis for treating refractory ovarian carcinoma with mifepristone. METHODS: DDP-resistant human ovarian carcinoma cell line SK-OV-3 cells were cultured in vitro, and the MTT assay was used to examine the antiproliferative effect of mifepristone with or without DDP on SK-OV-3 cells. The cooperative effects between mifepristone and DDP in inhibiting the growth of SK-OV-3 cells were analyzed. TdT mediated dUTP nick end labeling (TUNEL) and flow cytometry (FCM) were used to examine the effects of mifepristone with or without DDP on the apoptosis and cell cycle of SK-OV-3 cells. RESULTS: Mifepristone produced concentration-dependent antiproliferative effect on SK-OV-3 cells at all experimental concentrations.Enhanced antiproliferative effects were found when SK-OV-3 cells were cultured with mifepristone at 0.625, 1.25, 2.5, 5, 10, and 20 microg/ml combined with 1.25 microg/ml or 2.5 microg/ml DDP (q >1.15). Only additive effects were found when the cells were cultured with mifepristone and 0.625 microg/ml or 5.0 microg/ml DDP (0.85 1.15) and G0/G1-phase stasis. CONCLUSION: Mifepristone can inhibit the growth of chemo-resistant human ovarian carcinoma cells,and enhance its DDP sensitivity. This may be associated with the synergic effect between mifepristone and DDP in inducing apoptosis and G(0)/G(1)-phase stasis.