Adenovirus-mediated p53 growth inhibition of ovarian cancer cells is independent of endogenous p53 status

Objective. The aim of this study was to determine the effect of transfectio n of adenovirus-mediated wild-type p53 into ovarian cancer cells with both wild-type and mutant endogenous p53. Study design. Eight human ovarian cancer cell lines were used: three with p 53 mutations, one that is p53 null, and four with wild-type p53. The recomb inant p53 adenovirus (Adp53) contains the cytomegalovirus promoter, wild-ty pe p53 cDNA, and SV40 polyadenylation signal in a minigene cassette inserte d into the E1-deleted region of modified Ad5. The transduction efficiency o f cells was assessed using a beta-gal-containing adenovirus. Cell-counting assays were used to evaluate the effect of transfection with Adp53 on the g rowth of cells. P53 expression was evaluated using Western blot. Cell cycle analysis and apoptosis studies were done using a tunnel-based assay and fl uorescent activated cell sorting. Results. Transduction efficiencies varied between cell lines. More than 90% growth inhibition occurred in seven of eight cell lines after infection wi th adenovirus-mediated p53 if a viral dose leading to at least 50% of cells infected was used. Regardless of endogenous p53 status, apoptosis occurred in cells infected with p53. Conclusions. Ovarian cancer cells are growth inhibited by transfection with adenovirus-mediated p53 regardless of their endogenous p53 status. Growth inhibition is related to transduction efficiency. (C) 1999 Academic Press.