靶向抑制转录因子FOXA1对前列腺癌细胞增殖的影响及机制研究  

Effect of targeted inhibition of transcription factor FOXA1 on the proliferation of prostate cancer cells and its mechanism

作　　者：瞿小祥 鲁小红 QU Xiaoxiang;LU Xiaohong(Department of Urology,Xianning Central Hospital,Xianning 437100,Hubei,China)

机构地区：[1]咸宁市中心医院泌尿外科,湖北咸宁437100

出　　处：《中国性科学》2020年第5期1-3,共3页Chinese Journal of Human Sexuality

摘　　要：目的研究靶向抑制转录因子叉头框蛋白A1(FOXA1)对前列腺癌细胞增殖的影响及机制。方法培养人前列腺癌细胞株PC3M,随机分为转染FOXA1 siRNA的FOXA1组、转染空载体siRNA的空白对照组。转染siRNA 24小时后,测定细胞的增殖活力及细胞中FOXA1、雄激素受体(AR)通路基因、p27Kip1通路基因的表达水平。结果FOXA1组细胞中细胞的增殖活力值以及FOXA1、AR、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、哺乳动物雷帕霉素靶蛋白(mTOR)、β-连环蛋白(β-catenin)、细胞周期蛋白(Cyclin)D1、CyclinE、细胞周期蛋白依赖性激酶(CDK)2、CDK4、CDK6的mRNA相对表达水平均低于空白对照组,差异具有统计学意义(均P<0.05);p27Kip1的mRNA相对表达水平高于空白对照组,差异具有统计学意义(P<0.05)。结论靶向抑制FOXA1对前列腺癌细胞增殖具有抑制作用,调节AR通路和p27Kip1通路的活化是前列腺癌细胞增殖受抑制的分子机制。Objective To investigate the effects and mechanisms of targeted inhibitory transcription factor foxhead box A1(FOXA1)on the proliferation of prostate cancer cells.Methods Human prostate cancer cell line PC3 M was cultured and randomly divided into FOXA1 group transfected with FOXA1 siRNA and blank control group transfected with empty vector siRNA.After 24 hours of siRNA transfection,the proliferation activity of cells and the expression levels of FOXA1,androgen receptor(AR)pathway genes and p27 Kip1 pathway genes were measured.Results Cell proliferation activity and the relative expression levels of FOXA1,AR,phosphatidylinositol 3-kinase(PI3 K),protein kinase B(AKT),mammalian rapamycin target protein(mTOR),β-catenin,Cyclin D1,Cyclin E,cyclin dependent kinase 2(CDK2),CDK4 and CDK6 in FOXA1 group were lower than those of the blank control group,with statistically significant differences between the two groups(all P<0.05).And the relative mRNA expression level of p27 Kip1 was higher than that of the blank control group,with statistically significant differences between the two groups(P<0.05).Conclusions Targeted inhibition of FOXA1 can inhibit the proliferation of prostate cancer cells,and regulating the activation of AR pathway and p27 Kip1 pathway is the molecular mechanism responsible for inhibition of prostate cancer cell proliferation.

关 键 词：前列腺癌 叉头框蛋白A1 增殖 雄激素受体 P27^KIP1 

分 类 号：R697[医药卫生—泌尿科学]