靶向肝癌表达p16基因的腺病毒载体对裸鼠移植瘤的抗癌活性

Antitumor efficacy of the adenoviral vector expressing p16 gene targeting the hepatocellular carcinoma models on nude mice

目的:利用已构建好的在肝癌细胞中定向表达p16基因的腺病毒载体AdAFP-p16,研究腺病毒介导p16基因的表达对肝癌裸鼠移植瘤的抗癌活性。方法:培养肝癌细胞SMMC-7721,于裸鼠右侧腹部近腋下皮肤注射1×106细胞数细胞悬液,建立裸鼠肝癌移植瘤模型。成瘤后给于瘤体内AdAFP-p16病毒注射治疗,病毒总量1×109pfu/只,观察AdAFP-p16对肝癌模型的抗肿瘤疗效以及p16基因表达引起的肝癌细胞病理变化。结果:AdAFP-p16能够介导p16基因在肝癌细胞中特异性表达,具有明显的肿瘤生长抑制作用,抑制率可达60.12%(P<0.01),引起肝癌细胞的坏死。结论:AFP启动子控制的p16基因在肝癌细胞中定向表达,能够抑制肝癌模型的生长,对肝癌综合治疗具有重要意义。

Objective：To investigate the expression of pl6 gene specifically in hepatocellular carcinoma models on nude mice and the antitumor efficacy of this adenoviral vector, by using the previously constructed adenovirus, AdAFP-p16, which expresses p16 gene and targets hepatocellular carcinoma. Methods： The hepatocellular carcinoma cell line, SMMC-7721, was cultured and injected （ 1 x 10^6 cells/mouse） subcutaneously on the right flanks of nude mice to establish the xenograft models. AdAFP-pl6 of 1 xl0^9 pfu/mouse dosage was administrated intratumorally,then the in v ivo antitumor activity of AdAFP-pl6 was measured,and the morphological changes were observed pathologically. Results：AdAFP-pl6 can mediate pl6 gene expression specifically in hepatocellular carcinoma cells,and obviously inhibit the growth of hepatocellular carcinoma cells on nude mice,with the inhibition rate of 60.12%. Tumor necrosis was observed after the treatment of AdAFP-pl6. Conclusion：The AFP promoter could control pl6 gene expression specifically in hepatocellular carcinoma. This approach obviously inhibited the growth of the hepatocellular carcinoma xenografts on nude mice, and might play an important role in the comprehensive therapy for hepatocellular carcinoma.