Objective: To investigate the effects of mifepristone on cell proliferation of human androgen-independent prostate carcinoma cell lines DU-145, PC-3 in vitro and the possible mechanisms involved.
Methods: The A values of the prostate cancer cells DU-145 and PC-3 in each group with various concentrations (1, 10, 50, 100 micromol/L) of mifepristone at various time intervals (24-120 h) were detected with the colorimetric 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl tetrazolium bromide assay. The apoptosis rates of the DU-145 and PC-3 cells treated with 10 micromol/L of mifepristone for 24 h and 48 h were assessed by flow cytometry analysis technique. Immunohistochemical technique was used to determine the expression of bax, bcl-2 and vascular endothelial growth factor (VEGF) proteins after treatment with 10 micromol/L of mifepristone.
Results: The A values of the cancer cells treated with 1 micromol/L of mifepristone were similar to that of controls, while those of the cells treated with 10 micromol/L, 50 micromol/L and 100 micromol/L of mifepristone were significantly different from that of controls (P < 0.01). Mifepristone markedly inhibited cell proliferation of prostate cancer cells DU-145 and PC-3 on a dose- and time-depending manner. The apoptosis rates of 10 micromol/L mifepristone for DU-145 cell line at 24 h, 48 h were respectively 15.3%, 30.4% with flow cytometry method and then PC-3 cell line were respectively 22.2%, 32.0%. Immunohistochemical technique showed the expression of bcl-2 and VEGF in the DU-145 and PC-3 cells treated with 10 micromol/L of mifepristone were significantly decreased, and the expression of bax was increased.
Conclusions: Mifepristone can induce apoptosis of androgen-independent prostate cancer cell lines DU-145 and PC-3 in vitro. The apoptosis effect is time-and-dose dependent. Mifepristone could initiate a cell death command via apoptotic pathways decreasing the expression of VEGF protein, downregulating the expression of bcl-2 protein and increasing the expression of bax protein.