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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/10330
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| Title: | Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-kappaB signaling |
| Other Titles: | Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-κB signaling |
| Authors: | Chiang, CF;Chao, TT;Su, YF;Hsu, CC;Chien, CY;Chiu, KC;Shiah, SG;Lee, CH;Liu, SY;Shieh, YS |
| Contributors: | National Institute of Cancer Research |
| Abstract: | 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. |
| Date: | 2017-03 |
| Relation: | 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 |
| Appears in Collections: | [夏興國] 期刊論文
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