节点文献
胞嘧啶脱氨酶基因与前体药物5-氟胞嘧啶对人肝癌的基因治疗作用(英文)
Gene therapy for human hepatocellular carcinoma with cytosine deaminase gene and prodrug flucytosine
【摘要】 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。
【Abstract】 AIM: To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine ( Hu, 5-fluorocytosine ) on human hepatocellular carcinoma. METHODS: CD gene was transduced into human hepatocellular carcinoma cell line SMMC7721 with retroviral method and the cytotoxicity of Flu on the tumor cells was assayed in vitro with clonogenic techniques. The xenograft tumor model in nude mice was used to study in vivo therapeutic effects of CD gene/Flu system against human hepatocellular carcinoma. RESULTS: CD gene/Flu system had significant antitumor activities on human hepatocellular carcinoma cells in vitro and in nude mice. The antitumor activities of Flu 500 mg· kg-1 on hepatocellular carcinoma xenografts in nude mice were more potent than those of 5-fluouracil 10 mg·kg-1. CD gene/Flu system possessed bystander killing effects on hepatocellular carcinoma xenografts in nude mice. CONCLUSION: The experiment demonstrates the potential value of the CD gene/Flu system in the treatment of human hepatocellular carcinoma.
【Key words】 gene therapy; gene transfer; experimental liver neoplasm; prodrugs; antineoplastic agents; hepatocellular carcinoma; cultured tumor cells; nude mice; flucytosine;
- 【文献出处】 Acta Pharmacologica Sinica ,中国药理学报(英文版) , 编辑部邮箱 ,1999年05期
- 【分类号】R735.7
- 【下载频次】4