慢病毒载体介导survivin小分子干扰核糖核酸对裸鼠肺癌移植瘤的影响

Inhibitory effect of lentiviral vectors expressing small interfering RNA targeting survivin gene on growth of implanted human lung carcinoma in nude mice

目的观察慢病毒载体介导的survivin小分子干扰核糖核酸(small interfering RNA,siRNA)能否在裸鼠体内抑制肺癌移植瘤的生长。方法裸鼠随机分为3组,分别将A549细胞、无关序列及survivin siRNA慢病毒载体感染A549细胞接种于裸鼠右侧背部近腋窝皮下,观察survivin siRNA对移植瘤生长的影响。采用逆转录酶聚合酶链反应和Western blotting测定移植瘤组织survivin基因及其蛋白表达。结果成功建立人肺癌裸鼠皮下移植瘤模型。survivin siRNA组移植瘤体积及质量明显低于其他2组(P<0.01),抑瘤率为63.6%(基于体积)或58.8%(基于质量),survivin mRNA和蛋白表达分别减少53.7%、57.6%。结论慢病毒载体介导survivin siRNA可明显下调裸鼠体内survivin基因表达,抑制肺癌移植瘤的生长。

Objective To observe the effects of the lentiviral vectors expressing small interfering RNA （siRNA） for survivin gene in inhibiting human lung carcinoma A549 cell growth and its tumorigenicity in nude mice. Methods Nude mice were randomly divided into 3 groups, and A549 cells transfected with survivin siRNA and unrelated sequence lentiviral vectors or not transfected were subcutaneously inoculated into armpit tissues of mice to establish lung carcinoma mouse mo- dels. The influence of survivin siRNA on the implanted tumor growth was observed. Expressions of survivin protein and mRNA in implanted lung carcinoma tissues were detected by Western blotting and RT-PCR. Results Implanted human lung carcinoma mouse model was successively established. The tumor volume and weight in survivin siRNA group were markedly lower than those in unrelated sequence and A549 groups （P〈0. 01 ） . The tumor inhibitory rate in survivin siRNA group was 63.6% （based on volume） or 58.8% （based on weight）. Transfection of survivin siRNA significantly decreased the expression of survivin mRNA and protein in implanted lung carcinoma tissues by 53.7% and 57.6% respectively. Conclusion The lentiviral vectors expressing survivin siRNA can significantly inhibit survivin gene expression and suppress the tumorigenicity of A549 ceils in nude mice.