EXPERIMENTAL STUDIES OF USING ADENOVIRUS-MEDIATED CD/5-FC SUICIDE GENE IN TREATMENT OF PAN- CREATIC CANCER / 解放军医学杂志

ABSTRACT

The purpose of this study was to evaluate the killing effects of CD/5-FC suicide gene system mediated by adenovirus vector on human pancreatic carcinoma. Recombinant adenoviruses containing cytosine deaminase(CD) gene were constructed by the homologous recombination method in bacteria. The newly recombinated Ad-CD containing green fluorescent protein (GFP) was propagated in 293 cells and purified by cesium chloride gradient centrifugatioa Human pancreatic carcinoma cell line was infected with this virus, then 5-FC was added, and XTT assay was used to estimate relative numbers of viable cells. A heterotopic human pancreatic adenocarcinoma was successfully established in the flank of Balb/c nude mice. Adenoviral liquid containing CD gene was directly injected into xenografts following administration of 5-FC to observe the antitumor effects. Positive clones were selected by using endonuclease to digest the recombinants and the concentration of viral liquid containing CD gene was 2 1011 pfu/ml. It was found that significant cytotoxic activities were possessed by 5-FC for CD gene-transduced pancreatic carcinoma cells, but there was little effect on nontransduced ones. The anticancer effect was seen in vivo in xenografts of nude mice with in situ CD gene transduction. Our conclusian is that CD gene mediated by adenovirus has a high infectivity and is efficient for gene therapy of pancreatic carcinoma. These data demonstrate the therapeutic efficacy of an enzyme prodrug strategy in treatment of experimental pancreatic