四环素调控livin RNA干扰系统对肺癌移植瘤生长的影响  

Suppressive effect of Tet-on mediated livin RNA interference on growth of lung carcinoma xenegraft in a rat model

作　　者：李鸿茹[1,2] 涂洵崴 翁丽红 陈愉生 LI Hongru1,2, TU Xunwei1, WENG Lihong1, CHEN Yusheng1,2(1. Department of Respiratory and Critical Care Medicine, Fujian Provin- cial Hospital, Provincial Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian, China; 2. Research Institute of Four Respiratory Diseases of Fujian Province, Fuzhou 350001, Fujian, Chin)

机构地区：[1]福建医科大学省立临床医学院福建省立医院呼吸与危重症医学科,福建福州350001 [2]福建省呼吸四病研究室,福建福州350001

出　　处：《中国肿瘤生物治疗杂志》2018年第3期236-239,共4页Chinese Journal of Cancer Biotherapy

基　　金：福建省自然科学基金资助项目(No.2015J01376);福建省立医院优秀青年医师项目(No.2014YNQN03)~~

摘　　要：目的:探讨四环素调控(Tet-on)livin RNA干扰系统对肺癌移植瘤生长的影响,以期寻找更优的肺癌干预调控系统。方法:构建Tet-on livin shRNA慢病毒载体,在裸鼠右上肢背部皮下注射肺腺癌A549株细胞建立肺癌裸鼠皮下移植瘤模型,以Tet-on livin shRNA慢病毒载体注射瘤体干预livin表达,并以四环素腹腔注射诱导处理,了解Tet-on调控livin RNA干扰效果并观察其抑制肺癌细胞增殖情况。结果:经四环素诱导,Tet-on livin RNA组移植瘤组织中livin蛋白表达明显低于CTL组及Tet-onNC组,且Tet-on-livin RNA组瘤体质量明显低于CTL组及Tet-on-NC组[(5.31±0.86)vs(8.22±0.63)、(7.17±0.54)g,P<0.05];提示该调控系统可显著下调livin的表达,并抑制肺癌皮下移植瘤的生长,且该调控系统毒副作用小,未发现裸鼠死亡。结论:Tet-on livin RNA干扰系统在四环素诱导下可抑制肺癌生长,具有靶向性、可调控的特点,为以livin蛋白为靶点的肺癌靶向治疗研究提供重要的研究工具。Objective： To investigate he effect of tetracycline-（Tet-on） mediated livin RNA interference on growth of lung carcinoma xenegrafts, and find a better regulatory way to interfere the development on lung cancer. Methods： livin shRNA lentiviral vectors were constructed; and the lung cancer A549 cells were subcutaneously injected into right upper back of nude mice to establishxenegraft model. The livin shRNA lentiviral vectors were injected into xenografts to interfere the expression of livin, then tetracycline was injected intraperitoneally for the induction. The suppressive effect of Tet-on mediated livin RNA interference efficiency was investigated and lung cancer xenograft development was observed. Results： After the induction with Tet-on, livin gene expression was significantly inhibited by livin shRNA compared with the control group and Tet-on-NC group; the xenograft volume in Tet-on-livin shRNA group was significantly smaller than that in control group and Tet-on-NC group（[5.31±0.86]g vs [8.22±0.63]g and [7.17±0.54] g, P0.05）. Moreover, little body toxicity was observed and no nude mice died in this study. Conclusion： The Tet-on mediated livin shRNA could suppress the growth of lung cancer development with good targeting and controllable characteristics, which might provide a potent tool for treating lung cancer with livin protein as target.

关 键 词：LIVIN基因 四环素调控 RNA干扰 肺癌 A549细胞 动物模型 

分 类 号：R734.2[医药卫生—肿瘤] R730.5[医药卫生—临床医学]