[关键词]
[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-on- NC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。
[Key word]
[Abstract]
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 cancerA549 cells were subcutaneously injected into right upper back of nude mice to establish xenegraft mod- el. The livin shRNA lentiviral vectors were injected into xenografts to interfere the expression of livin, then tetracycline was injected in- traperitoneally 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 signifi- cantly 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, P<0.05). Moreover, lit- tle 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.
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[基金项目]
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)。