miR-200c通过激活Wnt/β-连环蛋白信号通路诱导膀胱癌细胞阿霉素耐药  

miR-200c induces resistance to doxorubicin through the Wnt/β-catenin signaling pathway in bladder cancer cells

作　　者：刘雷[1] 李轶枭 万波[1] 曾青[1] LIU lei;LI Yixiao;WAN Bo;ZENG Qing(Department of Urology, Third Xiangya Hospital of Central South University, Changsha 410008, Hunan, China)

机构地区：[1]中南大学湘雅三医院泌尿外科

出　　处：《中国临床药理学与治疗学》2018年第5期510-516,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖南省自然科学基金项目(13JJ2016)

摘　　要：目的:探讨miR-200c表达与膀胱癌细胞阿霉素(DOX)耐药的关系。方法:过表达或抑制miR-200c表达后,检测DOX对膀胱癌细胞(RT4、RT112、T24和TCCSUP)生长抑制作用的变化。Western blot检测miR-200c对Wnt/β-连环蛋白信号通路的影响,检测Wnt/β-连环蛋白信号激活剂Wnt3a干预对miR-200c诱导膀胱癌DOX耐药作用的影响。结果:抗miR-200c转染后,T24和RT4细胞DOX的耐药性显著下降。DOX干预后,与对照组细胞相比,抗miR-200c转染组膀胱癌细胞凋亡和S期积累明显增加。此外,抗miR-200c转染组膀胱癌细胞中Dkk1,Kremen2和s FRP2等Wnt/β-连环蛋白信号的负调控蛋白表达明显升高,Wnt/β-连环蛋白信号通路活性明显下降。Wnt3a干预能够拮抗抗miR-200c转染的膀胱癌细胞生长抑制作用。结论:miR-200c表达与膀胱癌细胞DOX耐药密切相关,且Wnt/β-连环蛋白信号通路激活介导了miR-200c诱导的膀胱癌细胞DOX耐药性。AIM： To investigate the relationship between miR-200 c expression and the response to DOX in bladder cancer cells. METHODS： Changes in the growth-inhibitory effect of DOX on bladder cancer cells（ RT4,RT112,T24 and TCCSUP） were examined after overexpression or suppression of miR-200 c. The effect of miR-200 c on the Wnt/β-catenin signaling pathway were also examined to investigate whether the altered growth-inhibitory effect by miR-200 c suppression was weakened after the addition of Wnt3 a,a Wnt/β-catenin signaling activator. RESULTS： RT4 and T24 cells transfected with antimiR-200 c showed significantly lower resistance to DOX. In the anti-miR-200 c-transfected cells,DOX induced significantly larger numbers of apoptotic cells and S phase accumulation compared to control cells,demonstrated by Annexin V assay and flow cytometric analysis of the cell cycle,respectively. The transfected cells showed overexpression of putative target molecules including Dkk1,Kremen2 and s FRP2 and lower activation of the Wnt/β-catenin signaling pathway.The addition of Wnt3 a weakened the augmented growth-inhibitory effect of anti-miR-200 c transfection. CONCLUSION： miR-200 c expression correlates significantly with the growth-inhibitory effect of DOX and that activation of the Wnt/β-catenin signaling pathway mediates the miR-200 c-induced resistance to DOX in bladder cancer cell lines.

关 键 词：膀胱癌 阿霉素 微小核糖核酸 MIR-200C Wnt/β-连环蛋白信号通路 

分 类 号：R965.2[医药卫生—药理学]