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Int. J. Mol. Sci. 2016, 17(12), 2000; doi:10.3390/ijms17122000

Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells

Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, Taiyuan 030000, China
Author to whom correspondence should be addressed.
Academic Editors: Gianni Sava and Alberta Bergamo
Received: 10 September 2016 / Revised: 19 November 2016 / Accepted: 22 November 2016 / Published: 30 November 2016
(This article belongs to the Special Issue Chemical and Molecular Approach to Tumor Metastases)
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Background: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. Methods: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay. Western blotting was performed to detect E-cadherin, vimentin, signal transducer and activator of transcription 3 (STAT3), snail family transcriptional repressor 2 (SNAIL2), phosphorylation of p70s6k (p-p70s6k) and -Pyruvate kinase M2 (PKM2) Results: TGF-β1 promoted proliferation and migration, and it attenuated apoptosis compared with cells treated with metformin with or without TGF-β1 in cervical carcinoma cells. Moreover, metformin partially abolished TGF-β1-induced EMT cell proliferation and reversed TGF-β1-induced EMT. In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor. Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression. Conclusion: Metformin abolishes TGF-β1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression. Our study provides a novel mechanistic insight into the anti-tumor effects of metformin. View Full-Text
Keywords: metformin; mammalian target of rapamycin; epithelial-mesenchymal transition; PKM2 metformin; mammalian target of rapamycin; epithelial-mesenchymal transition; PKM2

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cheng, K.; Hao, M. Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells. Int. J. Mol. Sci. 2016, 17, 2000.

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