Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation

Osteosarcoma (OS) is the most common cancer that affects the bone and appears to be resistant to several chemotherapeutic drugs. The aim of the present study was to verify whether the combination of metformin and cisplatin has an effect on OS cell lines. OS cell lines U2OS, 143B and MG63 were treated with metformin, cisplatin or a combination of both drugs. Viability, apoptosis and cell cycle were evaluated to characterize the effects of the treatments. Western blot analyses were used to evaluate protein expression. All OS cell lines were found to be sensitive to metformin with different values of IC50, showing a slowdown of cell cycle associated or not with apoptosis. In particular, metformin was able to sensitize cells to cisplatin, to which all OS cell lines were resistant, demonstrating a synergistic effect in the combined treatment of the two drugs. The data obtained may have clinical relevance for novel therapeutic strategies for the treatment of OS; metformin inhibits tumor cell growth and amplifies the effect of cisplatin.