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目的:探讨胞嘧啶脱氨酶基因(CD)与前体药物5-氟胞嘧啶(Flu)对肝癌的抗肿瘤作用,方法:应用逆转录病毒法,将CD基因转导入肿瘤细胞,体外应用克隆分析法测定Flu对肿瘤细胞的细胞毒性;应用裸鼠移植瘤模型研究CD基因/Flu体系对肝癌的抗肿瘤作用,结果:前体药物Flu对人肝癌在体外和裸鼠体内具有明显的抗癌作用.与5-氟尿嘧啶10 mg·kg~(-1)相比,前体药物Flu 500 mg·kg~(-1)对裸鼠肝癌移植瘤有更强的抗癌作用.CD基因/Flu对人肝癌裸鼠移植瘤具有旁观者杀伤效应.结论:CD基因/Flu体系在治疗肝癌中有潜在的价值。
Objective: To investigate the antitumor effect of cytosine deaminase gene (CD) and 5-fluorocytosine (Flu) on hepatocellular carcinoma. Methods: The retroviral method was used to transduce the CD gene into tumor cells and cloned in vitro. Analytical method was used to determine the cytotoxicity of Flu on tumor cells. The tumor xenograft model was used to study the anti-tumor effect of CD gene/Flu system on hepatocellular carcinoma. Results: The prodrug Flu has obvious anti-cancer effect on human hepatoma in vitro and in nude mice. Effect. Compared with 5-fluorouracil 10 mg·kg -1 , the prodrug Flu 500 mg·kg -1 has a stronger anticancer effect on human hepatocellular carcinoma xenografts in nude mice. CD gene/Flu pair Human hepatocellular carcinoma xenografts in nude mice have bystander killing effect. Conclusion: CD gene/Flu system has potential value in the treatment of hepatocellular carcinoma.