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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Inhibitory effects of interferon-gamma plasmid DNA on DMBA-TPA induced mouse skin carcinogenesis
1Department of Veterinary Infectious Diseases, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
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.
Insights
Hydrodynamics-based gene therapy effectively uses interferon-gamma (IFN-γ) DNA to treat skin cancer in mice. This method reduced tumors and suppressed cancer cell growth without causing liver damage.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interferon-gamma (IFN-γ) possesses tumor-suppressive properties.
- IFN-γ gene therapy is a potential strategy for treating skin cancer.
- Hydrodynamics-based gene delivery offers a method for in vivo gene transfection.
Purpose of the Study:
- To evaluate the efficacy of hydrodynamics-based interferon-gamma (IFN-γ) gene transfection for skin cancer treatment.
- To assess the safety and therapeutic effects of this gene therapy approach in a mouse model.
Main Methods:
- Induced skin carcinogenesis in mice using 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate.
- Administered plasmid DNA encoding IFN-γ into the tail vein via hydrodynamics-based transfection.
- Monitored serum IFN-γ levels, liver toxicity, papilloma development, epidermal cell proliferation, and apoptosis.
Main Results:
- Substantially elevated serum IFN-γ levels were achieved without observable liver toxicity.
- Mice treated with IFN-γ plasmid DNA showed a significant reduction in papilloma numbers.
- Suppressed epidermal cell proliferation and induced caspase-3-mediated apoptosis were observed in the treated group.
Conclusions:
- Hydrodynamics-based transfection of IFN-γ plasmid DNA is a safe and effective method for skin cancer gene therapy.
- This approach demonstrates potential for in vivo tumor suppression and treatment of skin malignancies.
