An inducible recombinant adenoviral vector encoding Bax selectively induces apoptosis in ovarian cancer cells

A variety of strategies have been developed to accomplish gene therapy for cancer. One of these approaches is mutation compensation, whereby gene transfer is used for abrogating the function of dysregulated dominant oncogenes or for restoration of the function of deficient tumor suppressor genes. Bax, a member of the Bcl-2 family that can act as a tumor suppressor, potently induces apoptosis by caspase-dependent and independent mechanisms. We were able to generate a recombinant adenoviral vector encoding bax by using the inducible Cre-loxP system. Bax expression was tightly induced specifically by Cre recombinase, therefore allowing viral production. Furthermore, expression of Bax resulted in apoptotic cell death in human ovarian cancer cells. In contrast, Bax-mediated cell death was not observed in normal human peritoneal mesothelial cells. These results indicate that production and delivery of Bax via recombinant adenovirus vector is feasible, and that its preferential killing effect in human ovarian cancer cells might allow its use for gene therapy of ovarian cancer.