【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。更多还原

【Abstract】 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-diphenyltetrazolium bromide assay. The apoptosis rates of the DU-145 and PC-3 cells treated with 10 μmol/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 μmol/L of mifepristone. Results The A values of the cancer cells treated with 1 μmol/L of mifepristone were similar to that of controls, while those of the cells treated with 10 μmol/L, 50 μmol/L and 100 μmol/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,downregulating the expression of bcl-2 protein and increasing the expression of bax protein.更多还原