Metformin inhibits the proliferation and metastasis of osteosarcoma cells by suppressing the phosphorylation of Akt

Li,Zuohong; Wang,Lesheng; Luo,Nan; Zhao,Yantao; Li,Jiazhi; Chen,Qiwei; Tian,Yu

doi:10.3892/ol.2018.8297

Metformin inhibits the proliferation and metastasis of osteosarcoma cells by suppressing the phosphorylation of Akt

Authors:
- Zuohong Li
- Lesheng Wang
- Nan Luo
- Yantao Zhao
- Jiazhi Li
- Qiwei Chen
- Yu Tian
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Affiliations: Department of Orthopedics, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China, Department of Blood Transfusion, Chinese People's Liberation Army 210 Hospital, Dalian, Liaoning 116015, P.R. China, Department of Infectious Diseases, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Department of Pathology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: March 20, 2018 https://doi.org/10.3892/ol.2018.8297
Pages: 7948-7954

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Abstract

Metformin (Met) is a therapeutic agent for the treatment of type 2 diabetes mellitus. There is evidence that Met may reduce the risk of cancer in patients with type 2 diabetes mellitus by inhibiting tumor cell growth, prolonging the overall survival time in patients with various types of malignancy. However, the function and mechanism of Met have not been fully elucidated in osteosarcoma (OS). The present study evaluated the anti‑proliferative effect of Met on MG63 and U2OS OS cells, identifying that it acted in a dose‑ and time‑dependent manner. Met also inhibited OS cell migration and invasion, potentially by regulating the epithelial‑mesenchymal transition in OS cells. Mechanistically, Met was demonstrated to partly exert these functions through the suppression of Akt phosphorylation, which was associated with increased phosphatase and tensin (PTEN) expression. Silencing PTEN prevented the Met‑induced inhibition of the growth and metastasis of OS cells. As Met has anti‑proliferative and anti‑metastatic effects on OS cells it is a potential candidate, in combination with other chemotherapeutic agents, for use in the treatment of OS.

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