Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells.

ABSTRACT

BACKGROUND/AIM: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells. MATERIALS AND METHODS: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells. RESULTS: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins. CONCLUSION: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.