Pim-2抑制前列腺癌细胞凋亡信号通路的研究  

Pim-2 signal pathway inhibits apoptosis of prostate cancer cells

作　　者：任轲[1] 苟欣[1] 康简[1] REN Ke;GOU Xin;KANG Jian(Department of Urology,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China)

机构地区：[1]重庆医科大学附属第一医院泌尿外科,重庆400016

出　　处：《第三军医大学学报》2019年第4期323-330,共8页Journal of Third Military Medical University

基　　金：重庆市卫生与计划生育委员会面上项目(2011-2-038);重庆市科委基础与前沿计划一般项目(CSTC2016jcjA0099)~~

摘　　要：目的探讨癌基因Pim-2抑制前列腺癌细胞凋亡的机制及其信号通路。方法分别检测前列腺癌组织及前列腺增生组织中Pim-2及其下游信号通路因子的表达,通过RNAi技术分别沉默前列腺癌细胞株中Pim-2或XIAP表达,通过基因转染技术增强非肿瘤性前列腺上皮细胞中Pim-2或XIAP表达,检测eIF4B磷酸化水平及XIAP表达水平,测定细胞凋亡率。结果 Pim-2在前列腺癌组织及细胞株中的表达显著高于前列腺增生组织及非肿瘤性前列腺细胞株(P <0. 05);在非肿瘤性前列腺细胞株中转染Pim-2后,其Pim-2表达水平显著增高,eIF4B磷酸化水平及XIAP表达水平也同时显著增高,而细胞凋亡率则显著降低(P <0. 05);在前列腺癌细胞株中转染Pim-2 SiRNA后,Pim-2表达水平显著减低,eIF4B磷酸化水平及XIAP表达水平也同时显著降低,而细胞凋亡率则显著增高(P <0. 05);在高表达Pim-2及XIAP的前列腺癌细胞株中转染XIAP SiRNA沉默其表达后,细胞凋亡率显著增高(P <0. 05);在低表达Pim-2及XIAP的非肿瘤性前列腺细胞株中转染XIAP增强其表达后,细胞凋亡率无明显变化。结论 Pim-2在前列腺癌细胞中异常高表达; Pim-2可通过磷酸化eIF4B促进XIAP表达,抑制细胞凋亡;仅当Pim-2与XIAP同时高表达时才能抑制前列腺癌细胞凋亡。Objective To explore the mechanism by which Pim-2 signal pathway inhibits apoptosis of prostate cancer cells.Methods We examined the expression levels of Pim-2 and the downstream factors in prostate cancer tissues,benign prostatic hyperplasia tissues,prostate cancer cell lines and prostatic epithelial cells.In prostate cancer DU-145 cell line with Pim-2 or XIAP silencing using RNA interference technique and in non-neoplastic prostatic epithelial cell line RWPE-1 over-expressing Pim-2 or XIAP via gene transfection,we detected the phosphorylation level of eIF4 B and the expression of XIAP and examined the apoptosis rate of the cells.Results Pim-2 was significantly over-expressed in prostate cancer tissues and prostate cancer cell lines as compared with benign prostatic hyperplasia tissue and non-neoplastic prostatic epithelial cells.RWPE-1 cells over-expressing Pim-2 showed significantly increased phosphorylation level of eIF4 B with enhanced XIAP expression and a significantly lowered apoptosis rate.DU-145 cells with Pim-2 silencing exhibited significantly lowered phosphorylation level of eIF4 B and XIAP expression with obviously increased cell apoptosis rate.XIAP silencing in DU-145 cells that over-expressed Pim-2 and XIAP caused a significant increase in the cell apoptosis rate;XIAP over-expression in RWPE-1 cells with low expressions of Pim-2 and XIAP did not cause significant changes in the cell apoptosis rate.Conclusion Pim-2 is over-expressed in prostate cancer cells.Pim-2 may inhibit the apoptosis of prostate cancer cells through phosphorylating eIF4 B to promote XIAP expression,and this inhibitory effect occurs only when both Pim-2 and XIAP are over-expressed in prostate cancer cells.

关 键 词：PIM-2 前列腺癌 凋亡 

分 类 号：R394.2[医药卫生—医学遗传学] R730.23[医药卫生—基础医学]