米非司酮诱导雄激素非依赖性前列腺癌细胞凋亡的实验研究  

Induction of apoptosis by mifepristone in androgen-independent prostate cancer cell lines in vitro

作　　者：张辉[1] 吕家驹[1] 高庆贞[1] 张捷[2] 

机构地区：[1]山东大学山东省立医院泌尿外科,济南250021 [2]山东大学山东省立医院中心实验室,济南250021

出　　处：《中华外科杂志》2006年第6期382-385,共4页Chinese Journal of Surgery

基　　金：国家自然基金资助项目(30471731)

摘　　要：目的探讨米非司酮在体外诱导雄激素非依赖性前列腺癌DU-145、PC-3细胞凋亡的作用。方法采用四甲基偶氮唑蓝法检测1，10，50和100μmol／L米非司酮作用于前列腺癌DU-145、PC-3细胞24～120h的吸光度（A）值，用流式细胞仪检测10μmol／L米非司酮作用24和48h后DU．145、PC-3细胞凋亡率的变化；采用免疫组化法检测米非司酮作用DU-145、PC．3细胞后bax、bcl-2、血管内皮生长因子（VEGF）蛋白表达的变化。结果1μmol／L米非司酮组的A值与对照组相比，差异无统计学意义（P〉0．05）；10，50和100μmol／L米非司酮组的A值与对照组比较，差异有统计学意义（P〈0．01）；米非司酮对前列腺癌DU-145、PC-3细胞的抑制作用呈时间-剂量依赖性。10μmol／L米非司酮作用前列腺癌DU-145细胞24和48h的凋亡率分别为15．3％和30．4％，PC-3细胞的凋亡率分别为22．2％和32．0％。经10μmol／L米非司酮作用后，DU-145、PC-3细胞中VEGF和bcl-2蛋白的表达明显减少，而bax的表达显著增加（P〈0．05）。结论米非司酮以时间．剂量依赖性方式抑制激素非依赖性前列腺癌DU-145和Pc-3细胞的增殖，其作用可能是通过降低VEGF蛋白的表达。从而下调bcl-2、激活bax蛋白的表达来实现。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 μmol/L） of mifepristone at various time intervals （24-120 h） were detected with the colorimetric 3-（ 4,5-dimethylthiazol-2-yl ） -2,5-diphenyltetrazo]ium bromide assay. The apoptosis rates of the DU-145 and PC-3 cells treated with 10μmoL/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 10μmoL/L of mifepristone. Results The A values of the cancer cells treated with 1μmol/L of mifepristone were similar to that of controls, while those of the cells treated with 10μmoL/L, 50μmoL/L and 100μmoL/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 μmol/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 μmoL/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, downregnlating the expression of bcl-2 protein and increasing the expression of hax protein.

关 键 词：米非司酮 前列腺肿瘤 脱噬作用 

分 类 号：R737.25[医药卫生—肿瘤] R73-36[医药卫生—临床医学]