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 tran sfer is used for abrogating the function of dysregulated dominant oncogenes or for restoration of the function of deficient tumor suppressor genes. Ba r, a member of the Bcl-2 family that can act as a tumor suppressor, potentl y induces apoptosis by caspase-dependent and independent mechanisms. We wer e able to generate a recombinant adenoviral vector encoding bar by using th e inducible Cre-loxP system. Bar expression was tightly induced specificall y by Cre recombinase, therefore allowing viral production. Furthermore, exp ression of Bar resulted in apoptotic cell death in human ovarian cancer cel ls. In contrast, Bar-mediated cell death was not observed in normal human p eritoneal mesothelial cells. These results indicate that production and del ivery of Bax via recombinant adenovirus vector is feasible, and that its pr eferential killing effect in human ovarian cancer cells might allow its use for gene therapy of ovarian cancer.