癌蛋白CIP2A在胃癌顺铂耐药中的表达及机制研究  

Expression and Mechanism of Oncoprotein CIP2A in Cisplatin Resistant in Gastric Cancer

作　　者：伍叶子 周彤 刘雪文 向雨晨 司渊 刘莹 WU Ye-zi;ZHOU Tong;LIU Xue-wen;XIANG Yu-chen;SI Yuan;LIU Ying(School of Basic Medical Sciences,Hubei University of Medicine,Shiyan,Hubei 442000,China;School of Biomedical Engineering,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院基础医学院,湖北十堰442000 [2]湖北医药学院生物医学工程学院,湖北十堰442000

出　　处：《湖北医药学院学报》2019年第6期515-521,543,F0002,共9页Journal of Hubei University of Medicine

基　　金：国家自然科学基金青年项目(81802387);十堰市科技局引导性项目(18Y13);湖北医药学院研究生科技创新项目(YC2019001);大学生创新创业训练计划项目(201910929015,201910929020)

摘　　要：目的:本文旨在探讨蛋白磷酸酶2A (cancerous inhibitor of protein phosphatase 2A,CIP2A)在顺铂(cisplatin,DDP)耐药的胃癌细胞中的表达及机制。方法:实时荧光定量PCR、免疫组化和Western blotting检测患者胃癌组织及细胞中CIP2A表达情况;CIP2A过表达质粒和siRNA分别转染SGC7901和SGC7901/DDP细胞,通过MTT法检测细胞对DDP的敏感性;流式细胞术用于检测细胞凋亡;实时荧光定量PCR、Western blotting检测多药耐药相关蛋白的表达。结果:与DDP敏感型患者相比,CIP2A在DDP耐药胃癌患者中表达较高,而CIP2A高表达的DDP耐药胃癌患者的总体生存率低于CIP2A低表达的患者。在DDP耐药的胃癌细胞中敲低CIP2A能够抑制细胞增殖、促进细胞凋亡,并且也可以提高DDP耐药细胞对DDP的敏感性,反之,CIP2A过表达则导致DDP耐药细胞对DDP的敏感性降低,以上作用是通过CIP2A影响多药耐药相关蛋白在胃癌细胞中的表达实现的。结论:CIP2A在胃癌顺铂耐药的发生中发挥着关键作用,有望成为DDP耐药胃癌患者的一种新型治疗靶点。Objective The purpose of this study was to investigate the expression and mechanism of cancerous inhibitor protein phosphatase 2 A(CIP2 A) in cisplatin(DDP) resistant gastric cancer cells. Methods Real-time quantitative PCR, immunohistochemical analysis, or western blotting were performed to detect CIP2 A expression in clinical gastric cancer tissues. SGC7901 and SGC7901/DDP cells were transfected with CIP2 A expression vector and siRNA respectively. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used to measure cell apoptosis. Real-time fluorescence quantitative PCR and Western blotting were used to detect the expression of multidrug resistance-related proteins. Results Compared with DDP-sensitive patients, CIP2 A was highly expressed in patients with DDP-resistant gastric cancer, while the overall survival rate of patients with DDP-resistant gastric cancer with high CIP2 A expression was lower than that of patients with low CIP2 A expression. Knockdown of CIP2 A in DDP-resistant gastric cancer cells can inhibit cell proliferation and promote apoptosis, and can also increase the sensitivity of DDP-resistant cells to DDP. Conversely, overexpression of CIP2 A can reduce the sensitivity of DDP-resistant cells to DDP. The above effect is achieved through CIP2 A affecting the expression of multidrug resistance-associated proteins in gastric cancer cells. Conclusion CIP2 A plays a key role in the development of cisplatin resistance in gastric cancer and is expected to become a new therapeutic target for patients with DDP-resistant gastric cancer.

关 键 词：CIP2A 胃癌 顺铂 化疗耐药性 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]