title: Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation.
abstract: 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.
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, I-40136 Bologna, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Quattrini
authors.forename: Amalia
authors.initials: A
authors.lastname: Conti
authors.forename: Laura
authors.initials: L
authors.lastname: Pazzaglia
authors.forename: Chiara
authors.initials: C
authors.lastname: Novello
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Benassi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D002945:Cisplatin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000096:biosynthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D011494:Protein Kinases / Q000096:biosynthesis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D008687:Metformin; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D055372:AMP-Activated Protein Kinases; D002945:Cisplatin