癌灶内注射腺病毒介导的血管内皮生长因子启动子-胸苷激酶基因治疗大鼠肝癌

目的研究腺病毒介导的血管内皮生长因子启动子调控的单纯疱疹病毒胸苷激酶基因(AdVEGF tk)对大鼠肝癌的治疗作用。方法以二乙基亚硝胺 (DEN)诱导Wistar大鼠产生肝癌 ,将成癌鼠随机分组 ,在同鼠肝内的多发性癌灶中选取 2个孤立的癌灶分别作为参照癌和处理癌 ,记录癌灶直径。参照癌不作处理。处理癌分别用不同的重组腺病毒癌内注射 ,并从次日起连续 10d每天腹腔内给予丙氧鸟苷 (GCV)或生理盐水 1次。停止注射后第 10天剖腹测量处理癌和参照癌大小 ,比较各组间癌灶体积增长率。结果用低浓度DEN处理 12 0d ,所有被探查的大鼠均有典型的肝癌形成。与同鼠中参照癌相比 ,AdVEGF tk/生理盐水处理的癌灶体积增长率平均值差异无显著意义 (P>0 0 5 ) ,而AdCMV tk/GCV和AdVEGF tk/GCV处理的癌灶体积增长率平均值显著降低 (P <0 0 1) ,与AdVEGF tk/生理盐水组处理癌和参照癌的体积增长率平均值之间的差异也有显著意义 (P<0 0 1)。AdVEGF tk/GCV处理癌与AdCMV tk/GCV处理癌体积增长率之间差异无显著意义 (P>0 0 5 )。结论癌灶内注射AdVEGF tk对大鼠肝癌生长具有明显抑制作用。

Therapeutic efficacy of adenovirus-mediated gene transfer of thymidine kinase coded with vascular endothelial growth factor promoter on murine experimental hepatocellular carcinoma

Objective To investigate the therapeutic efficacy of adenovirus-mediated transfer of thymidine kinase gene controlled by vascular endothelial growth factor promoter against of induced hepatocellular carcinoma in a rat model. MethodsMultiple hepatic neoplastic nodules in Wistar rats were chemically induced by diethylnitrosamine. Two relatively isolated neoplastic nodules of similar size were chosen in each rat to serve as control and to receive intratumor injection of recombinant adenovirus (AdVEGF-tk or AdCMV-tk), and the beginning on the second day ganciclovir (GCV) was given intraperitoneally for consecutive 10 days. Tumor size and tumor growth rates were compared between the two groups. Results There was no difference in the mean growth values between control tumors and AdVEGF-tk/saline-treated tumors( P > 0.05),and between AdCMV-tk/GCV- and AdVEGF-tk/GCV-treated tumors( P >0.05). The mean growth values in AdCMV-tk/GCV- and AdVEGF-tk/GCV-treated tumors were significantly lower than those in untreated tumors and AdVEGF-tk/saline-untreated tumors( P <0.01). Conclusion Intratumor injection of AdVEGF-tk followed by GCV administration impedes the growth of the hepatocellular carcinoma in a rat model.