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.
Keywords: Akt; metastasis; metformin; osteosarcoma; phosphatase and tensin homolog; proliferation.