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Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway
Han, Baiyu1,2; Cui, Hanzhi3; Kang, Lei4; Zhang, Xuelin5; Jin, Zhitao6; Lu, Lanmin1; Fan, Zhongyi1,2
关键词Metformin Thyroid Cancer Mtor Cell Proliferation Cell Migration Emt
刊名TUMOR BIOLOGY
2015-08-01
DOI10.1007/s13277-015-3315-4
36期:8页:6295-6304
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]ACTIVATED PROTEIN-KINASE ; EPITHELIAL-MESENCHYMAL TRANSITION ; IN-VITRO ; TGF-BETA ; OVARIAN-CANCER ; BRAF MUTATION ; STEM-CELLS ; VIVO ; METASTASIS ; SUPPRESSES
英文摘要

Mammalian target of rapamycin (mTOR) signaling pathways have been shown to be activated in thyroid cancer. Recent evidences have demonstrated that the antidiabetic agent metformin, an activator of 5′-AMP-activated protein kinase, can impair the proliferation and migration of cancer cells via inhibition of mTOR. However, the underlying mechanisms remain unclear. In this study, we show that metformin can inhibit mTOR pathway to impair growth and migration of the thyroid cancer cell lines. Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation. Metformin reduced epithelial to mesenchymal transition (EMT) in thyroid carcinoma cells. Moreover, metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin, and Snail. Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules. These results indicate that metformin can suppress the proliferation, migration, and EMT of thyroid cancer cell lines by inhibiting mTOR signaling. These findings suggest that metformin and its molecular targets may be useful in thyroid carcinoma therapy.

语种英语
WOS记录号WOS:000360193800066
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51214
专题北京大学第一临床医学院_核医学科
作者单位1.PLA, Hosp 309, Dept Oncol, Beijing, Peoples R China
2.Gen Hosp Second Artillery, Dept Cardiol, Beijing, Peoples R China
3.PLA, Hosp 264, Dept Endocrinol & Metab, Taiyuan 030000, Shanxi, Peoples R China
4.Peoples Liberat Army Gen Hosp, Dept Oncol, Beijing, Peoples R China
5.Peking Univ, Hosp 1, Dept Nucl Med, Beijing 100871, Peoples R China
6.Peoples Liberat Army Gen Hosp, Dept Respirat, Beijing, Peoples R China
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Han, Baiyu,Cui, Hanzhi,Kang, Lei,et al. Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway[J]. TUMOR BIOLOGY,2015,36(8):6295-6304.
APA Han, Baiyu.,Cui, Hanzhi.,Kang, Lei.,Zhang, Xuelin.,Jin, Zhitao.,...&Fan, Zhongyi.(2015).Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway.TUMOR BIOLOGY,36(8),6295-6304.
MLA Han, Baiyu,et al."Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway".TUMOR BIOLOGY 36.8(2015):6295-6304.
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