腺病毒介导双自杀基因CD／TK对人肝癌细胞株Bel7402的抑制作用

Efficacy of denovirus-mediated double suicide gene combined with prodrugs for treatment of human hepatocellular carcinoma

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 efficacy of recombinant adenovires containing cytosine diaminase/herpes simplex viros-1 thymidine kinase（CD/TK） for treatment of human hepatoeellular carcinoma. Methods Recombinated adenovirus Ad. CD/TK containing double suicide gene CD/TK infected human hepatocellular carcinoma BELT402, and in vitro cytotoxicity of GCV and 5-Fc in different concentration against BEL7402 were evaluated with MTT methods. The tumor growth suppression test were taken with nude mice BEL7402 subcutaneously model injected intratumorally with Ad. CD/TK combined with GCV （50 mg/kg）and 5-Fc（500 mg/kg）daily for 10 days. Results The IC50 of 5-Fc for QBC939 infected with Ad. CDTK was （223 ± 15） μmol/L, and the IC50 of GCV was （12.1 ± 2.3） μmol/L. Combination of GCV and 5-Fe against QBC939 infected with Ad. CD/TK had obvious synergie effects. Ad. CD/TK combined with GCV and 5-Fc significantly suppressed the growth of nude mice tumor model. Conclusion Recombinant adenovirus Ad. CD/TK combined with prodrug has a significant efficacy in treatment of human hepatocelluar carcinoma.