Gene therapy for human hepatocellular carcinoma with cytosine deaminase gene and prodrug flucytosine.

Zhongguo yao li xue bao = Acta pharmacologica Sinica Pub Date : 1999-05-01

H Z Lü, D Z Wu, Y L Wan, B Gu, H Z Gao, Y Q Liang, J X Wang

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Abstract

Aim: To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 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.

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胞嘧啶脱氨酶基因与前药氟胞嘧啶治疗人肝癌的研究。

目的:探讨胞嘧啶脱氨酶(CD)基因联合前药氟胞嘧啶(Flu, 5-氟胞嘧啶)对人肝癌的抗肿瘤作用。方法:用逆转录病毒法将CD基因转染人肝癌细胞系SMMC7721，用克隆技术测定流感病毒对肿瘤细胞的体外毒性。采用裸鼠异种移植瘤模型，研究CD基因/流感系统对人肝癌的体内治疗作用。结果:CD基因/流感系统对人肝癌细胞有明显的体外和裸鼠抗肿瘤活性。流感500毫克的抗肿瘤活性。Kg-1对裸鼠肝癌移植瘤的抑制作用强于5-氟尿嘧啶10 mg.kg-1。CD基因/流感系统对裸鼠肝癌移植具有旁观者杀伤作用。结论:本实验证明了CD基因/Flu系统在治疗人肝癌中的潜在价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Zhongguo yao li xue bao = Acta pharmacologica Sinica

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