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干扰素-γ质粒 DNA 对 DMBA-TPA 诱导的小鼠皮肤癌变的抑制作用。

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

机构信息

Department of Veterinary Infectious Diseases, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.

出版信息

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

DOI:10.1038/cgt.2011.36
PMID:21799530
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.

摘要

干扰素-γ(IFN-γ)具有生物活性,被认为在肿瘤抑制中具有重要作用。因此,IFN-γ 基因是体内细胞因子基因治疗皮肤癌的潜在候选基因。本研究评估了基于流体动力学的 IFN-γ 基因转染治疗皮肤癌的疗效,其中在二甲基苯并蒽(7,12-DMBA)和 12-O-十四烷酰佛波醇-13-醋酸盐诱导的皮肤癌变后,将编码 IFN-γ 的质粒 DNA 经尾静脉注入小鼠。IFN-γ 质粒 DNA 注射的小鼠血清 IFN-γ 水平显著升高,且无肝毒性。注射 IFN-γ 质粒 DNA 的小鼠皮肤肿瘤数量明显减少,表皮细胞增殖受到抑制,诱导 caspase-3 介导的细胞凋亡。这些结果表明,基于流体动力学的 IFN-γ 质粒 DNA 转染是一种方便有效的皮肤癌基因治疗方法。

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