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

Cancer Gene Ther. 2011 Sep;18(9):646-54. doi: 10.1038/cgt.2011.36. Epub 2011 Jul 29.

Abstract

Interferon-gamma (IFN-γ) exhibits biological activities that are considered to have important roles in tumor suppression. Therefore, the IFN-γ 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-γ gene transfection for skin cancer treatment, in which the plasmid DNA encoding IFN-γ 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-γ were substantially elevated without liver toxicity. The mice injected with IFN-γ 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-γ plasmid DNA is a convenient and efficient means of skin cancer gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation
  • Female
  • Genetic Therapy
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / therapy*
  • Tetradecanoylphorbol Acetate / toxicity*

Substances

  • 9,10-Dimethyl-1,2-benzanthracene
  • Interferon-gamma
  • Caspase 3
  • Tetradecanoylphorbol Acetate