丙泊酚对前列腺癌细胞增殖及雄激素转录活性的影响及其机制

Effects of Propofol on Proliferation and Androgen Transcriptional Activity of Prostate Cancer Cells and its Mechanism

【目的】探讨丙泊酚对二氢睾丸激素(DHT)刺激的前列腺癌细胞系(LNCaP)细胞增殖的影响及其机制。【方法】LNCaP细胞按照干预方式分为4组:对照组(生理盐水)、DHT组(10 nM DHT干预)、DHT+10 μM丙泊酚组(10 nM DHT+10 μM丙泊酚干预)和DHT+50 μM丙泊酚组(10 nM DHT+50 μM丙泊酚干预)。采用实时定量PCR检测各组细胞中雄激素依赖基因前列腺特异性抗原(PSA)、FK506结合蛋白5(FKBP5)和跨膜蛋白酶丝氨酸2(TMPRSS2)的水平,MTT法分析各组细胞存活情况,Western Blot检测各组细胞中AR和低氧诱导因子(HIF)的表达。【结果】与DHT组相比,DHT+10 μM丙泊酚组和DHT+50 μM丙泊酚组细胞中PSA、FKBP5和TMPRSS2基因的表达在作用24 h时均显著降低(P<0.05)。丙泊酚暴露12 h和24 h可显著抑制LNCaP细胞的增殖(P<0.05),而暴露4 h则无明显作用。与DHT组相比,DHT+10丙泊酚组和DHT+50 μM丙泊酚组细胞核中AR和HIF-1a蛋白的表达均显著降低(P<0.05)。【结论】丙泊酚抑制LNCaP细胞增殖,并抑制AR转录活性以此降低AR核蛋白水平。

【Objective】To investigate the effect of propofol on the proliferation of prostate cancer cell line(LNCaP)stimulated by dihydrotestosterone(DHT)and its mechanism.【Methods】LNCaP cells were divided into four groups according to the intervention mode:control group(normal saline),DHT group(10 nM DHT intervention),DHT+10 μM propofol group(10 nM DHT+10 μM propofol intervention)and DHT+50 μM propofol group(10 nM DHT+50 μM propofol intervention).Real time quantitative PCR was used to detect the levels of androgen dependent gene prostate specific antigen(PSA),FK506 binding protein 5(FKBP5)and transmembrane protease serine 2(TMPRSS2).MTT method was used to analyze the survival of cells in each group.Western blot was used to detect the expression of AR and hypoxia inducible factor(HIF)in cells in each group.【Results】Compared with the DHT group,the expression of PSA,FKBP5 and TMPRSS2 genes in the DHT+10 propofol group and the DHT+50 μM propofol group decreased significantly at 24 hours(P<0.05).Propofol exposure for 12 h and 24 h could significantly inhibit the proliferation of LNCaP cells(P<0.05),but exposure for 4 h had no significant effect.Compared with the DHT group,the expression of AR and HIF-1,protein in nucleus of the DHT+10 propofol group and the DHT+50 μM propofol group were significantly lower(F<0.05).【Conclusion】Propofol inhibits the proliferation of LNCaP cells and AR transcriptional activity,so as to reduce the level of AR nucleoprotein.