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

Abstract

Although replication-defective adenoviruses (Ads) are used as vectors for delivering 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 Ad vectors (Ad5-CMV-lacZ) affected cell kinetics in two different types of lung cancer cell line in 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 fashion. The slowed cell proliferation resulted from both increased cell death and slower cell cycle progression of the vector- infected cells. The morphology 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, apoptosis of vector-infected cells may also reduce transgene expression in cancer cells. Minimization of the induction of apoptosis of vector-infected cells is important for the prolongation of the transduction efficiency of Ad vectors.