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


CONCLUSIONS
The experiment demonstrates the potential value of the CD gene/Flu system in the treatment of human hepatocellular carcinoma.
Lü
H Z
HZ
Department of Clinical Pharmacology, Affiliated North Taiping Hospital, Chinese Academy of Medical Sciences, Beijing. luhz@usa.net
Wu
D Z
DZ
Wan
Y L
YL
Gu
B
B
Gao
H Z
HZ
Liang
Y Q
YQ
Wang
J X
JX
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy; D043525:Cytosine Deaminase; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use*; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011355:Prodrugs; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase