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

机译:干扰素-γ质粒DNA对DMBA-TPA诱导的小鼠皮肤癌变的抑制作用

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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.
机译:干扰素-γ(IFN-γ)具有生物学活性,被认为在肿瘤抑制中具有重要作用。因此,IFN-γ基因是针对皮肤癌的体内细胞因子基因治疗的潜在候选者。本研究评估了基于水动力学的IFN-γ基因转染治疗皮肤癌的功效,其中在7,12-二甲基苯并[a]蒽和12之后,将编码IFN-γ的质粒DNA给予小鼠尾静脉。 -O-十四烷酰phorbol-13-乙酸盐诱导的皮肤癌变。血清IFN-γ水平明显升高,无肝毒性。注射了IFN-γ质粒DNA的小鼠乳头状瘤数量明显减少,表皮细胞增殖受到抑制,caspase-3介导的细胞凋亡被诱导。这些结果表明,基于流体动力学的IFN-γ质粒DNA转染是皮肤癌基因治疗的方便和有效手段。

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