Gene therapy for murine liver cancer by adenovirus-mediated cytosine deaminase gene.
OBJECTIVE
To investigate anti-tumor effects of AdCD/5FC system on mice bearing MM45T.Li liver cancer.


METHODS
IC(50), bystander effect and cell apoptosis were observed in vitro. After treatment of the tumor with AdCD in situ and injection of 5FC peritoneally into the mice, the anti-tumor effects were observed.


RESULTS
When MOI=100, AdCD infected MM45T.Li was sensitive to 5FC, and the IC(50) was less than 50 micromol/L. When 10% MM45T.Li cells were infected with AdCD, 72% cells died after 5FC treatment, which showed significant bystander effect. Through TUNEL test and Hoechst 33258 staining, it was demonstrated that there was cell apoptosis after AdCD/5FC treatment of the MM45T.Li cell 21 day after treatment of the mice bearing tumor. The tumor volume was reduced significantly (F=20.33, P<0.05), and the median survival time was prolonged from 41-43 day to 49 day.


CONCLUSIONS
AdCD/5FC system shows significant anti-tumor effects.
Sun
W
W
Research Center for Human Gene Therapy. Department of Biochemistry & Molecular Biology, Shanghai Second Medical University, Shanghai 200025, China.
Wei
D
D
Tang
Z
Z
Chen
S
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000627:therapeutic use*; D015316:Genetic Therapy; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009700:Nucleoside Deaminases / Q000235:genetics*
D000963:Antimetabolites; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase