中山醫學大學機構典藏 CSMUIR:Item 310902500/10481
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    题名: GMI, an immunomodulatory protein from Ganoderma microsporum, induces autophagy in non-small cell lung cancer cells.
    作者: Hsin IL
    Ou CC
    Wu TC
    Jan MS
    Wu MF
    Chiu LY
    Lue KH
    Ko JL
    贡献者: 中山醫學大學
    日期: 2011-08
    上传时间: 2015-03-16T10:20:50Z (UTC)
    ISSN: 1554-8627
    摘要: Autophagy is a self-digestive process that degrades the cytoplasmic constituents. Immunomodulatory protein, one major bioactive component of Ganoderma, has antitumor activity. In this study, recombinant fungal immunomodulatory protein, GMI, was cloned from Ganoderma microsporum and purified. We demonstrated that GMI induces lung cancer cell death by activating autophagy, but does not induce apoptotic cell death. On western blot, GMI increased LC3 conversion and decreased p53 expression in a time- and concentration-dependent manner. Cytoplasmic calcium chelator BAPTA-AM was used to prove that GMI promotes autophagy via a calcium-mediated signaling pathway. 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the cytotoxicity of GMI on cell viability assay. Using VZV-G pseudotyped lentivirus-shRNA system for autophagy-related genes silencing, the capabilities of GMI to reduce cell viability and colony formation were abolished in autophagy-defective cells. Furthermore, GMI did not stimulate apoptosis after blocking of autophagy by 3-MA or shRNA knockdown system. In xenograft studies, oral administration of GMI inhibited the tumor growth and induced autophagy significantly in nude mice that had received a subcutaneous injection of A549 cells. This is the first study to reveal the novel function of GMI in activating autophagy. GMI may be a potential chemopreventive agent against non-small cell lung cancer.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10481
    http://dx.doi.org/10.4161/auto.7.8.15698
    關聯: Autophagy. 2011 Aug;7(8):873-82
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