國家衛生研究院 NHRI:Item 3990099045/10330
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    题名: Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-kappaB signaling
    其它题名: Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-κB signaling
    作者: Chiang, CF;Chao, TT;Su, YF;Hsu, CC;Chien, CY;Chiu, KC;Shiah, SG;Lee, CH;Liu, SY;Shieh, YS
    贡献者: National Institute of Cancer Research
    摘要: Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-alpha and attenuated M2-related cytokines IL-8, IL-10, and TGF-beta expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages. Conversely, M1 inducing cytokine IFN-gamma was upper-regulated in cancer cells. Additionally, through increasing AMPK and p65 phosphorylation, metformin treatment activated AMPK-NF-kappaB signaling of cancer cells that participate in regulating M1 and M2 inducing cytokines expression. Moreover, Compound C, an AMPK inhibitor, significantly increased IL-4, IL-10, and IL-13 expression while BAY-117082, an NF-kappaB inhibitor, decreased expression. In metformin-treated tumor tissue, the percentage of M2-like macrophages decreased while M1-like macrophages increased. These findings suggest that metformin activates cancer AMPK-NF-kappaB signaling, a pathway involved in regulating M1/M2 expression and inducing genes for macrophage polarization to anti-tumor phenotype.
    日期: 2017-03
    關聯: Oncotarget. 2017 Mar;8(13):20706-20718.
    Link to: http://dx.doi.org/10.18632/oncotarget.14982
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000397642400019
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85016390353
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