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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 si RNA转染组(皮下注射BEL-7402肝癌细胞,成瘤后瘤内注射survivin si RNA/LipDMEM转染混合物)、联合转染组(双自杀基因转染+survivin si RNA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 m RNA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 m RNA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。
OBJECTIVE: To investigate the inhibitory effect of Ad-KDRP-CD / TK and survivin gene mediated by adenovirus mediated by KDR promoter on the growth of hepatoma cells in nude mice. Methods: Twenty nude mice were randomly divided into model group (BEL-7402 hepatoma cells implanted into the tumor without any treatment), double suicide gene transfection group (subcutaneously transfected with Ad-KDRP-CD / TK BEL-7402 cells were injected intraperitoneally with prodrug ganciclovir and 5-fluorocytosine. Survivin si RNA was transfected into BEL-7402 hepatoma cells by intradermal injection of survivin si RNA / LipDMEM transfection mixture), combined transfection group (double suicide gene transfection + survivin si RNA transfection). After 2 weeks of treatment, the mice in each group were sacrificed and the tumor mass was weighed and the tumor inhibition rate was calculated. The microvessel density (MVD) and the expression of survivin m RNA and protein in tumor tissue were detected. Results: The tumor mass of each treatment group was significantly lower than that of the model group (all P <0.05), and the tumor inhibition rate of the combined transfection group was the highest (all P <0.05). The MVD, survivin m RNA and protein levels of tumor tissue were significantly decreased The combined transfection group showed the most obvious reduction (all P <0.05). Conclusion: The double suicide gene combined with survivin interference is an effective way to inhibit the growth of murine hepatoma cells in vivo.