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目的探讨含胞嘧啶脱氨酶(CD)／5-氟胞嘧啶(5-Fc)单纯疱疹病毒1型胸腺嘧啶激酶基因融合自杀基因(CD／TK)的重组腺病毒治疗肝癌的疗效。方法重组腺病毒Ad．CD／TK感染人肝癌细胞Bel7402,用噻唑蓝(MTT)方法观察不同浓度5-Fc和无环鸟苷(GCV)对其杀伤效应; 建立Bel7402裸鼠皮下移植瘤模型,瘤内注射Ad．CD／TK,腹腔注射GCV(50 mg／kg体重)和／或5- Fc(500 mg／kg体重)10 d,观察肿瘤生长抑制效应。结果在对感染Ad．CD／TK的Bel7402细胞的体外杀伤实验中,GCV的IC50为(12．1±2．3)μmol／L,5-Fc的IC50为(223±15)μmol／L,并且两者有协同效应。在Bel7402裸鼠移植瘤模型中,联合Ad．CD／TK和GCV、5-Fc能够显著抑制肿瘤的生长。结论腺病毒为载体的双自杀基因转染和前药的应用对人肝癌细胞的体内、体外治疗疗效明显。
Objective To investigate the therapeutic effect of recombinant adenovirus containing cytosine deaminase (CD) / 5-fluorocytosine (5-Fc) herpes simplex virus 1 type thymidine kinase gene fusion suicide gene (CD / TK) on hepatocellular carcinoma. Methods Recombinant adenovirus Ad. The Bel7402 cells were infected with CD / TK. The killing effect of 5-Fc and acyclovir (GCV) was observed by MTT assay. The Bel7402 subcutaneously transplanted tumor model was established in nude mice. The tumor growth inhibitory effect was observed by CD / TK, intraperitoneal injection of GCV (50 mg / kg body weight) and / or 5-Fc (500 mg / kg body weight) The result is when infected with Ad. The IC50 of GCV was (12.1 ± 2.3) μmol / L and the IC50 of 5-Fc was (223 ± 15) μmol / L in CD / TK Bel7402 cells in vitro and the synergistic effects . Bel7402 xenografts in nude mice combined with Ad. CD / TK and GCV, 5-Fc can significantly inhibit tumor growth. Conclusion Adenovirus-mediated double suicide gene transfection and the application of prodrugs have obvious therapeutic effects on human hepatocellular carcinoma cells in vitro and in vivo.