靶向阻断Snail逆转非小细胞肺癌多药耐药的研究  

Reversion of multidrug resistance of non-small cell lung cancer by targeted blocking Snail

作　　者：张丽娜[1] 刘菲[1] 孙磊[1] 田慧玲[1] 陈为一[1] 李洪利[2] 张宝刚[1] 尹崇高[3] 郭文君[1] 

机构地区：[1]潍坊医学院病理学教研室,261053 [2]潍坊医学院医学研究实验中心,261053 [3]潍坊医学院护理学院,261053

出　　处：《实用医学杂志》2014年第3期345-348,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81072068);山东省中青年科学家科研奖励基金(博士基金)项目(编号:2010BSB14050;BS2011YY060);山东省高等学校科技计划项目(编号:J12LK03;J13LK03);潍坊市科技局资助项目(编号:201104092;20112052);潍坊医学院青年科技创新基金(编号:K11QC1002)

摘　　要：目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)上皮-间质转化(epithelialmesenchymal transition,EMT)与多药耐药(multidrug resistance,MDR)基因的相互关系,为临床肺癌治疗提供实验和理论依据。方法:采用免疫组织化学SP法检测52例肺癌组织中Snail、P-糖蛋白(P-glycoprotein,P-gp)、肺耐药蛋白(lung resistance p rotein,LRP)的表达并分析它们的相关性。用RNA干扰技术稳定敲除肺腺癌细胞系A549中的Snail,采用Western blot法检测稳定转染后Snail蛋白的表达情况。Snail下降后,Western blot法检测P-gp、LRP蛋白表达情况。结果:Snail、P-gp、LRP在NSCLC组织中的表达率分别是73.1%、53.8%、51.9%,P-gp及LRP的蛋白表达与Snail的表达呈正相关。采用RNA干扰的方法成功敲除肺腺癌细胞系A549中Snail基因;A549细胞中Snail基因被敲除后耐药相关蛋白P-gp和LRP的表达明显降低。结论:在NSCLC中,Snail蛋白的表达与耐药相关基因的表达呈正相关;阻断肺癌细胞系A549细胞中的Snail能有效逆转肺癌的多药耐药特性。Objective To investigate the correlation between the epithelial-mesenchymal transition （EMT） and muhidrug resistance （MDR） gene in patients with non-small cell lung cancer （NSCLC）, and to provide experimental evidence for clinical treatment for NSCLC. Methods Immunohistochemistry SP method was used to detect the expressions of Snail, P-glycoprotein （P-gp） and lung resistance protein （LRP） in 52 patients with NSCLC, and their correlations were analyzed. Stable knockout of Snail in A549 cells by RNA interference was administered, and then Western blot was used to analyze the expressions of Snail, P-gp and LRP protein in A549 cells. Results The expression rates of Snail, P-gp and LRP in NSCLC tissues were 73.1%, 53.8% and 51.9%, respectively. The expression of Snail was significantly related to those of P-gp and LRP. Successful knockout of Snail gene in A549 cells by RNAi technology was observed, and then the expressions of P-gp and LRP were significantly down-regulated. Conclusion In NSCLC, the expression of Snail protein is significantly associated with MDR related zene. Blockin~ the expression of Snail can effectively reverse the MDR in A549 cells.

关 键 词：癌 非小细胞肺 转录因子 SNAIL 上皮一间质转化 P-gp LRP 

分 类 号：R734.2[医药卫生—肿瘤]