目的： 探讨腺病毒介导的KDR 启动子驱动的CD/TK 双自杀基因系统（Ad-KDRP-CD/TK） 联合 survivin 基因干扰对肝癌细胞在裸鼠体内生长的抑制作用。 方法：将20 只裸鼠随机分均为模型组（皮下植入BEL-7402 肝癌细胞成瘤，不加任何处理）、双自杀 基因转染组（皮下植入转染Ad-KDRP-CD/TK 的BEL-7402 细胞，成瘤后瘤内注射前药更昔洛韦与5- 氟 胞嘧啶）、survivin siRNA 转染组（皮下注射BEL-7402 肝癌细胞，成瘤后瘤内注射survivin siRNA/Lip- DMEM 转染混合物）、联合转染组（双自杀基因转染+survivin siRNA 转染处理）。治疗2 周后处死各组 小鼠，称取肿瘤质量，计算肿瘤抑制率，检测瘤组织微血管密度（MVD）及survivin mRNA 与蛋白表达。 结果：各治疗组的肿瘤质量明显小于模型组（均P<0.05），且联合转染组的抑瘤率最大（均P<0.05）； 肿瘤组织MVD、survivin mRNA 与蛋白水平均明显降低， 且联合转染组的降低程度最为明显（ 均 P<0.05）。 结论：双自杀基因联合survivin 干扰是抑制鼠肝癌细胞在体内生长的有效途径。
Double suicide gene system driven by KDR promoter combined with survivin gene interference on inhibiting the growth of hepatocellular carcinoma cells in vivo
Objective: The investigate the inhibitory effect of the adenovirus-mediated CD/TK double suicide gene system driven by KDR promoter (Ad-KDRP-CD/TK) combined with survivin gene interference on the growth of hepatocellular carcinoma (HCC) cells in nude mice. Methods: Twenty nude mice were equally randomized into model group (subcutaneous implantation of HCC BEL-7402 cells to establish xenograft tumor without other additional treatment), double suicide gene transfection group (subcutaneous implantation of BEL-7402 cells transfected with Ad-KDRP-CD/TK, followed by intratumor injection with the prodrug gancilovir and 5-fluorocytosine after tumor formation), survivin siRNA transfection group (subcutaneous implantation of BEL-7402 cells, followed by intratumor injection with survivin siRNA/Lip- DMEM transfection complex after tumor formation), and combination transfection group (double suicide gene transfection plus survivin siRNA transfection). Two weeks after transfection treatment, mice in each group were sacrificed, tumor weight and tumor inhibition rate were measured, the microvessel density (MVD), and survivin mRNA and protein expressions in the tumor tissues were determined. Results: In each treatment group compared with model group, the tumor weight was significantly reduced, with the maximum tumor inhibition in combination transfection group (all P<0.05); the MVD, and the expression levels of survivin mRNA and protein were significantly decreased, with the maximum decreasing amplitude in combination transfection group (all P<0.05). Conclusion: Double suicide gene combined with survivin gene interference is an effective method to inhibit the growth of HCC cells in vivo.