Recombinant E1-deleted adenovirus vector induces apoptosis in two lung cancer cell lines

Although replication-defective adenoviruses (Ads) are used as vectors for d elivering therapeutic genes to cancer cells, various effects of the viruses on the proliferation of lung cancer cells have been reported. Experiments were carried out to determine whether or not E1-deleted Ads vec tors (Ad5-CMV-lacZ) affected cell kinetics in two different types of lung c ancer cell Line irt vitro. A dose-dependent relationship was measured between the vector multiplicity of infection (MOI) and the efficiency of lacZ gene transfer to lung cancer cells. The growth curves of vector-infected cells were shifted to the right compared with those of vehicle-exposed cells in a vector MOI-dependent fas hion. The slowed cell proliferation resulted from both increased cell death and slower cell cycle progression of the vector-infected cells. The morpho logy of vector-exposed cells revealed apoptotic features including nuclear condensation and fragmented nuclei. These results indicate that using a higher vector MOI causes a higher gene transfer rate, but may induce apoptosis of infected cells. Although vector- induced apoptosis may be advantageous in inhibiting tumour growth, apoptosi s of vector-infected cells may also reduce transgene expression in cancer c ells. Minimization of the induction of apoptosis of vector-infected cells i s important for the prolongation of the transduction efficiency of Ad vecto rs.