Inhibitory effects of interferon-gamma plasmid DNA on DMBA-TPA induced mouse skin carcinogenesis

Interferon-gamma (IFN-gamma) exhibits biological activities that are considered to have important roles in tumor suppression. Therefore, the IFN-gamma gene is a potential candidate for in vivo cytokine gene therapy against skin cancer. The present study evaluated the efficacy of a hydrodynamics-based IFN-gamma gene transfection for skin cancer treatment, in which the plasmid DNA encoding IFN-gamma was administered into the tail vein of mice following 7,12-dimethylbenz[a] anthracene and 12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis. Serum levels of IFN-gamma were substantially elevated without liver toxicity. The mice injected with IFN-beta plasmid DNA displayed a marked reduction in papilloma numbers, suppressed proliferation of epidermal cells and induction of caspase-3-mediated apoptosis. These results suggest that the hydrodynamics-based transfection of IFN-gamma plasmid DNA is a convenient and efficient means of skin cancer gene therapy. Cancer Gene Therapy (2011) 18, 646-654; doi: 10.1038/cgt.2011.36; published online 29 July 2011