Enhanced antitumor activity of epirubicin combined with cerulenin in osteosarcoma

Osteosarcoma (OS) is the most common primary malignant neoplasm in children and adolescents. Epirubicin is one of the chemotherapeutic agents currently used for the treatment of OS; however, the efficacy of chemotherapy is hampered by the acquired drug resistance of OS. Cerulenin, an inhibitor of fatty acid synthase, has been defined as a candidate tumor suppressor. In this study, we explored the combined effect of cerulenin plus the chemotherapy drug, epirubicin, on human OS U2-OS cells in vitro and in vivo. We demonstrated that cerulenin plus epirubicin induced synergistic growth inhibition and enhanced apoptosis in U2-OS cells. We also demonstrated that cerulenin plus epirubicin synergistically suppressed tumor growth in subcutaneously xenografted U2-OS cells in athymic nude mice. Our results indicate that cerulenin enhances the anti-OS effects of epirubicin in vivo and in vitro.