Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on medulloblastoma cell line, Daoy, harboring mutant p53

To improve the survival rate, gene therapy, such as the replacement of inac tivated tumor suppressor genes, has become a new investigational adjuvant t reatment modality for human malignancies. We investigated the effect of ade novirus(Ad)-mediated transfer of wild-type p53 tumor suppressor gene on the medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50 multiplicity of infection (moi), immunohistochemical staining with p53 mon oclonal antibody showed positive staining in all cells 2 days after Ad-CMV- p53 infection. The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected cells, and expression of wild-type p53 protein peaked on day 2 after the infection. The growth of Ad-CMV-p53-infected cells was g reatly suppressed in vitro, and the Ad-CMV-p53 treatment significantly redu ced the tumor mass in vivo. The mean weight of Ad-CMV- infected tumors was only 16% of these which were mock infected, and 25% of those which were Ad- CMV-beta -gal infected. On microscopic examination, Ad-CMV-p53-infected tum ors showed numerous apoptotic bodies. This Ad-CMV-p53 gene transfer showed high transduction efficacy and expression, resulting in significant growth inhibition of Daoy harboring mutant type p53.