腺病毒介导的胞嘧啶脱氨酶基因对小鼠肝癌的治疗  

Gene therapy for murine liver cancer by adenovirus-mediated cytosine deaminase gene

作　　者：孙文长[1] 魏道严[1] 唐展云[1] 陈诗书[1] 

机构地区：[1]上海第二医科大学人类基因治疗研究中心,200025

出　　处：《中华肝脏病杂志》2000年第5期282-284,共3页Chinese Journal of Hepatology

基　　金：国家自然科学基金!39730440

摘　　要：目的探讨腺病毒介导的胞嘧啶脱氨酶基因对小鼠肝癌的基因治疗效果。方法分离纯化AdCD，体外实验观察IC_(50)，旁观者效应及凋亡现象。在体内，AdCD瘤内注射并腹腔注射5FC，观察AdCD／5FC系统对肝癌荷瘤小鼠的抗肿瘤效应。结果当MOI＝100时，AdCD感染的MM45T.Li细胞对5FC敏感,IC_(50)＜50μmol／L。与AdCD感染的MM45T.Li细胞占10％时，可有72％细胞死亡,AdCD／5FC系统对MM45T.Li细胞有明显的旁杀伤效应。TUNEL检测及Hoechst33258荧光染色证实AdCD／5FC系统可以诱导部分MM45T.Li细胞凋亡。荷瘤小鼠经过治疗21d后，各对照组肿瘤体积均数为2303～2943mm^3，治疗组AdCD／5FC组肿瘤体积（365±81）mm^3，ASdCD／5FC系统治疗小鼠肝癌，可以明显减小肿瘤体积（F＝20.33，P＜0.05）.对照组中位生存期41～43d,治疗组中位生存期49d。结论AdCD／5FC系统对小鼠肝癌有明显的治疗作用。Objective To investigate anti-tumor effects of AdCD/5FC system on mice bearing MM45T.Li livercancer. Methods IC50, bystander effect and cell apoptosis were observed in vitro. Atier treatment of the tumor with AdCDin situ and injection of 5FC peritoneally into the mice. the anti-tumor efttcts were observed. Results When MOI=100,AdCD infected MM45T.Li was sensitive to 5FC. and the IC50 was less than 50μmol/L. When 10% MM45T.Li cells wereinfected with AdCD, 72% cells died after 5FC treatment. which showed significant bystander effect. Through TUNEL testand Hoechst 33258 staining, it was demonstrated that there was cell apoptosis after AdCD/5FC treatment of the MM45T.Licell 21 d after treatment of the mice bearing tumor. The tumor volume was reduced significantly (F = 20.33, P < 0.05), and themedian survival time was prolonged from 41 ~43 d to 49 d. Conclusion AdCD/5FC system shows significant anti-tumoreffects.[

关 键 词：腺病毒 肝细胞癌 基因治疗 胞嘧啶脱氨酶 

分 类 号：R735.7[医药卫生—肿瘤]