Growth suppression of human ovarian carcinoma OV-MZ-2a and OV-MZ-32 cells mediated by gene transfer of wild-type p53 enhanced by chemotherapy in vitro

Purpose: The aim of this work was to observe the growth and chemosensitivit y of human ovarian cancer OV-MZ-2a and OV-MZ-32 cells following adenovirus- based wild-type p53 (Ad-p53) gene transfer alone or combined with chemother apeutic agents. Methods: Transduction efficiency was determined with a repo rter construct of adenovirus galactosidase by staining with 5-bromo-4-chlor o-3-indolyl beta-D-galactoside. For growth inhibition, OV-MZ-2a or OV-MZ-32 cells were infected with Ad-p53 particles at a multiplicity of infection ( m.o.i.) of 0.2-20, alone or combined with the chemotherapeutic agents taxol , cisplatin, doxorubicin or mitomycin C. Growth inhibition (assayed by tryp an blue exclusion), target gene expression (by Western blotting) and clonog enicity (by soft-agar assay) were determined following Ad-p53 transfer. Res ults: High transduction efficiency was observed following adenovirus galact osidase gene transfer; 94% of OV-MZ-2a cells and 69% of OV-MZ-32 cells expr essed the transgene. Following transfer of Ad-p53 into the two cell lines, a high level of p53 expression was detected after 12, 24, 48, 72 and 96 h i n OV-MZ-2a cells. At a m.o.i of 20, 96% and 90% growth inhibition were achi eved in OV-MZ-2a cells and OV-MZ-32 cells respectively. Clonogenicity was l ost completely in both cell lines following wild-type p53 transfer. Meanwhi le, Ad-p53 gene transfer combined with taxol, cisplatin, doxorubicin or mit omycin C was shown to be even more effective in suppressing growth in the t wo cell lines. Conclusions: Our results may suggest that wild-type p53 gene transfer mediated by an adenoviral vector is a potential strategy for trea ting ovarian cancer, and a combination of Ad-p53 gene transfer and chemothe rapeutic agents may be an even better treatment of the cancer.