Induction of apoptosis by mifepristone in androgen-independent prostate cancer cell lines in vitro.
- Author:
Hui ZHANG
1
;
Jia-ju LÜ
;
Qing-zhen GAO
;
Jie ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Androgens; metabolism; Apoptosis; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; Colorimetry; Dose-Response Relationship, Drug; Flow Cytometry; Hormone Antagonists; pharmacology; Humans; Male; Mifepristone; pharmacology; Prostatic Neoplasms; metabolism; pathology; Proto-Oncogene Proteins c-bcl-2; metabolism; Time Factors; Vascular Endothelial Growth Factor A; metabolism; bcl-2-Associated X Protein; metabolism
- From: Chinese Journal of Surgery 2006;44(6):382-385
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSThe 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.
RESULTSThe 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.
CONCLUSIONSMifepristone 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.