[Induction of apoptosis by mifepristone in androgen-independent prostate cancer cell lines in vitro].
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.
Zhang
Hui
H
Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
Lü
Jia-ju
JJ
Gao
Qing-zhen
QZ
Zhang
Jie
J
D000728:Androgens / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000728:Androgens; D006727:Hormone Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D015735:Mifepristone