Original Articles

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

Huang-zhang Lv, De-zheng Wu, Yong-ling Wan, Bin Gu, Hong-zhi Gao, Yue-qin Liang, Jia-xi Wang


To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 5-fluorocytosine) on human hepatocellular carcinoma.
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.
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.
The experiment demonstrates the potential value of the CD gene/Flu system in the treatment of human hepatocellular carcinoma.

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