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Tumor Biology

, Volume 36, Issue 8, pp 6295–6304 | Cite as

Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway

Research Article

Abstract

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.

Keywords

Metformin Thyroid cancer mTOR Cell proliferation Cell migration EMT 

Notes

Acknowledgments

The authors wish to thank Dr. JT Dou for his help and support.

Conflicts of interest

None

Supplementary material

13277_2015_3315_MOESM1_ESM.pdf (34 kb)
Supplementary Fig. 1 (PDF 34 kb)
13277_2015_3315_MOESM2_ESM.pdf (802 kb)
Supplementary Fig. 2 (PDF 801 kb)
13277_2015_3315_MOESM3_ESM.pdf (487 kb)
Supplementary Fig. 3 (PDF 487 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismThe 264 Hospital of PLATaiyuanChina
  2. 2.Department of OncologyPLA General HospitalBeijingChina
  3. 3.Department of Oncology309th Hostital of PLABeijingChina
  4. 4.Department of Nuclear MedicinePeking University First HospitalBeijingChina
  5. 5.Department of RespirationPLA General HospitalBeijingChina
  6. 6.Department of CardiologyGeneral Hospital of the Second ArtilleryBeijingChina

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