siRNA沉默CXCR4基因对胃癌生物学行为的影响  

Effect of Silencing CXCR4 Gene by siRNA on Biological Behavior of Gastric Cancer

作　　者：陈建荣 朱光辉 CHEN Jianrong;ZHU Guanghui(Department of General Surgery,Shanghai Fengxian District Central Hospital,Shanghai,201499;Department of General Surgery,Shanghai Public Health Clinical Center,Shanghai)

机构地区：[1]上海市奉贤区中心医院普外科,201499 [2]上海市公共卫生临床中心普外科

出　　处：《胃肠病学》2018年第10期597-601,共5页Chinese Journal of Gastroenterology

基　　金：上海市奉贤区科委课题(项目编号:奉科20131402)

摘　　要：背景:CXCR4在肿瘤细胞中广泛表达,参与肿瘤侵袭和转移。RNA干扰技术可有效降低或关闭基因的表达,从不同水平阻断肿瘤侵袭和转移。目的:研究胃癌组织中CXCR4 mRNA和蛋白表达及其与临床病理特征的关系,并探讨siRNA沉默CXCR4表达对胃癌生物学行为的影响。方法:选取86例胃癌及其癌旁正常黏膜组织,应用RTPCR和蛋白质印迹法分别检测CXCR4 mRNA和蛋白表达,并分析其与临床病理特征的关系。构建CXCR4干扰RNA质粒载体,并转染胃癌MKN45细胞。应用MTT法、Transwell法、流式细胞术分别评估胃癌细胞增殖、迁移和侵袭、凋亡能力。结果:胃癌组织中CXCR4 mRNA和蛋白表达明显高于癌旁正常组织(P <0. 05),且其表达与TNM分期、肿瘤分化、淋巴结转移相关(P <0. 05)。与阴性对照组相比,siRNA转染组转染24、48、72 h后MKN45细胞增殖力均显著降低(P <0. 05),迁移率和侵袭率均显著降低(P <0. 05),细胞凋亡率显著升高(P <0. 05)。结论:CXCR4在胃癌发展过程中具有重要作用;以siRNA沉默CXCR4基因后,可显著抑制MKN45细胞增殖,抑制体外细胞迁移和侵袭,促进细胞凋亡,从而为胃癌的治疗提供新策略。Background： CXCR4 is widely expressed in tumor cells and participates in tumor invasion and metastasis. RNA interference technology can effectively reduce or shut down the expression of genes and block tumor invasion and metastasis at different levels. Aims： To investigate the mRNA and protein expressions of CXCR4 and their relationship with clinicopathological features of gastric cancer, and to explore the effect of silencing CXCR4 by siRNA on biological behavior of gastric cancer. Methods： A total of 86 gastric cancer tissues and their adjacent normal mucosa were collected. mRNA and protein expressions of CXCR4 were detected by RT-PCR and Western blotting, respectively, and their relationship with clinicopathological features was analyzed. The CXCR4 RNA interference plasmid vector was constructed, and were transfected into gastric cancer cell line MKN45. Cell proliferation, migration and invasion, apoptosis were detected by MTT assay, Transwell assay and flow cytometry, respectively. Results： mRNA and protein expressions of CXCR4 in gastric cancer tissues were significantly higher than those in adjacent normal tissues （ P 〈0.05）, and CXCR4 expression was related to TNM staging, tumor differentiation, lymph node metastasis （ P 〈0.05）. Compared with negative control cells, cell proliferation in siRNA transfection group at 24, 48, and 72 hours were significantly decreased （ P 〈0.05）, cell migration rate and cell invasion rate were significantly decreased （ P 〈0.05）, and cell apoptosis rate was significantly increased （ P 〈0.05）. Conclusions： CXCR4 plays an important role in the development of gastric cancer. The silencing CXCR4 gene by siRNA can significantly inhibit the proliferation, migration and invasion of MKN45 cells, and increase apoptosis, thereby providing a new strategy for the treatment of gastric cancer.

关 键 词：胃肿瘤 受体 CXCR4 RNA 小分子干扰 细胞增殖 细胞迁移 细胞侵袭 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]