PURPOSE: The aim of this work was to observe the growth and chemosensitivity 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 chemotherapeutic agents. METHODS: Transduction efficiency was determined with a reporter construct of adenovirus galactosidase by staining with 5-bromo-4-chloro-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 trypan blue exclusion), target gene expression (by Western blotting) and clonogenicity (by soft-agar assay) were determined following Ad-p53 transfer. RESULTS: High transduction efficiency was observed following adenovirus galactosidase gene transfer; 94% of OV-MZ-2a cells and 69% of OV-MZ-32 cells expressed 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 in OV-MZ-2a cells. At a m.o.i of 20, 96% and 90% growth inhibition were achieved in OV-MZ-2a cells and OV-MZ-32 cells respectively. Clonogenicity was lost completely in both cell lines following wild-type p53 transfer. Meanwhile, Ad-p53 gene transfer combined with taxol, cisplatin, doxorubicin or mitomycin C was shown to be even more effective in suppressing growth in the two cell lines. CONCLUSIONS: Our results may suggest that wild-type p53 gene transfer mediated by an adenoviral vector is a potential strategy for treating ovarian cancer, and a combination of Ad-p53 gene transfer and chemotherapeutic agents may be an even better treatment of the cancer.
PURPOSE: The aim of this work was to observe the growth and chemosensitivity of humanovarian cancer OV-MZ-2a and OV-MZ-32 cells following adenovirus-based wild-type p53 (Ad-p53) gene transfer alone or combined with chemotherapeutic agents. METHODS: Transduction efficiency was determined with a reporter construct of adenovirus galactosidase by staining with 5-bromo-4-chloro-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 trypan blue exclusion), target gene expression (by Western blotting) and clonogenicity (by soft-agar assay) were determined following Ad-p53 transfer. RESULTS: High transduction efficiency was observed following adenovirus galactosidase gene transfer; 94% of OV-MZ-2a cells and 69% of OV-MZ-32 cells expressed 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 in OV-MZ-2a cells. At a m.o.i of 20, 96% and 90% growth inhibition were achieved in OV-MZ-2a cells and OV-MZ-32 cells respectively. Clonogenicity was lost completely in both cell lines following wild-type p53 transfer. Meanwhile, Ad-p53 gene transfer combined with taxol, cisplatin, doxorubicin or mitomycin C was shown to be even more effective in suppressing growth in the two cell lines. CONCLUSIONS: Our results may suggest that wild-type p53 gene transfer mediated by an adenoviral vector is a potential strategy for treating ovarian cancer, and a combination of Ad-p53 gene transfer and chemotherapeutic agents may be an even better treatment of the cancer.