Effect Of Mifepristone On The Growth And Chemosensitivity To Cisplatin On Human Endometrial Carcinoma Cell Line HEC-1-B

Objective: To investigate the effect and its mechanism of mifepristone on the growth and on chemosensitivity to cisplatin of human endometrial carcinoma cells in vitro.Methods: Human endometrial carcinoma cell line HEC-1-B cells,which were treated with various concentration of mifepristone or cisplatin or both, were cultured in vitro. Cell proliferation was evaluated by MTT assay. The cell cycle of HEC-1-B cells were analyzed by PI straining flow cytometry. The expression of Bcl-2 and Ki-67 protein in HEC-1-B cells were detected by immunohistochemistry.Results: (1) HEC-1-B cells, which were treated with 1.25 mg/L or 2.5mg/L Mifepristone, were not obviously changed. When Mifepristone 5mg/L～20mg/L, the proliferation of cells were obviously suppressed in time-dose dependent fashion in vitro. 1.25 mg/L or 2.5 mg/L Mifepristone significantly increased the cytotoxicity of cisplatin at concentrations 1.0～4.0mg/L to HEC-1-B cells(p<0.05).Their combination is synergistic, q>1.15.(2) PI staining flow cytometry data showed when 5 mg/L～20 mg/L mifepristone treated the cell for 24 hours, G0/G1 phase cell was significantly higher, while S phase cell was lower(p<0.05或p<0.01)in dose dependent fashion. Mifepristone(1.25mg/L, 2.5 mg/L) promoted cisplatin(2.5mg/L) to induce HEC-1-B cells apoptosis, G0/G1 phase cell was significantly higher in combination group than that in singly group, while S phase cell was lower(p<0.05) in comparison. G0/G1 phase and S phase were no significant in combination of different concentrations of mifepristone. (3) Immunohistochemistry indicated that the expression levels of bcl-2, ki-67 protein was no significant difference, when HEC-1-B cells were treated with 1.25mg/L or 2.5 mg/L mifepristone. Bcl-2 and Ki-67 were decreased at≥5 mg/L mifepristone(p<0.05). In combination of 1.25mg/L or 2.5 mg/L mifepristone and 2.5mg/L cisplatin the expression of bcl-2 and ki-67 was lower than that in singly group.Conclutions: Mifepristone≥5mg/L can inhibits the proliferation of HEC-1-B cells and induce the cell apoptosis in vitro,which can block cell cycle in G0/G1 phase. 1.25mg/L and 2.5mg/L mifepristone can enhance the effect of growth inhibition of cisplatin on HEC-1-B cells. Its mechanism may be related to block the cell cycle, regulate the expression of apoptosis-related gene, and promote apoptosis.