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

AIM: To investigate the antitumor effects of cytosine deaminase (CD) gene i n combination with prodrug flucytosine ( Flu, 5-fluorocytosine) on human he patocellular carcinoma. METHODS: CD gene was transduced into human hepatoce llular carcinoma cell Line SMMC7721 with retroviral method and the cytotoxi city of Flu on the tumor cells was assayed in vitro with clonogenic techniq ues. The xenograft tumor model in nude mice was used to study in vivo thera peutic 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 ac tivities of Flu 500 mg.kg(-1) on hepatocellular carcinoma xenografts in nud e mice were more potent than those of 5-fluouracil 10 mg.kg(-1). CD gene/Fl u system possessed bystander killing effects on hepatocellular carcinoma xe nografts in nude mice. CONCLUSION: The experiment demonstrates the potentia l value of the CD gene/Flu system in the treatment of human hepatocellular carcinoma.