KDR启动子驱动的CD/TK双自杀基因联合survivin基因干扰抑制肝癌细胞生长的体内研究  

Double suicide gene system driven by KDR promoter combined with survivin gene interference on inhibiting the growth of hepatocellular carcinoma cells in vivo

作　　者：杨六成[1] 吴凯[1] 黄宗海[1] 徐帅[1] 王健俊[1] 赵海军[1] 

机构地区：[1]南方医科大学珠江医院普通外科,广东广州510282

出　　处：《中国普通外科杂志》2015年第1期57-62,共6页China Journal of General Surgery

摘　　要：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： 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 xenograt 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-l uorocytosine at er tumor formation）, survivin si RNA transfectiongroup（subcutaneous implantation of BEL-7402 cells, followed by intratumor injection with survivin si RNA/LipDMEM transfection complex after tumor formation）, and combination transfection group（double suicide gene transfection plus survivin si RNA transfection）. Two weeks after transfection treatment, mice in each group were sacrifi ced, tumor weight and tumor inhibition rate were measured, the microvessel density（MVD）, and survivin m RNA 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 P0.05）; the MVD, and the expression levels of survivin m RNA and protein were significantly decreased, with the maximum decreasing amplitude in combination transfection group（all P0.05）.Conclusion： Double suicide gene combined with survivin gene interference is an effective method to inhibit the growth of HCC cells in vivo.

关 键 词：癌 肝细胞 基因 转基因 自杀 RNA干扰 小鼠 裸 

分 类 号：R735.7[医药卫生—肿瘤]