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 transfection 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 p53 mutations, one that is p53 null, and four with wild-type p53. The recombinant p53 adenovirus (Adp53) contains the cytomegalovirus promoter, wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette inserted into the E1-deleted region of modified Ad5. The transduction efficiency of cells was assessed using a beta-gal-containing adenovirus. Cell-counting assays were used to evaluate the effect of transfection with Adp53 on the growth of cells. P53 expression was evaluated using Western blot. Cell cycle analysis and apoptosis studies were done using a tunnel-based assay and fluorescent activated cell sorting. Results. Transduction efficiencies varied between cell lines. More than 90% growth inhibition occurred in seven of eight cell lines after infection with 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.