Sorafenib induces apoptosis and inhibits NF-ĸB-mediated anti-apoptotic and metastatic potential in osteosarcoma cells

Abstract

Background/Aim: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-ĸB (NF-ĸB)-mediated anti-apoptotic and metastatic potential in OS in vitro. Materials and Methods: The effect of sorafenib on apoptotic signaling transduction, anti-apoptotic, and metastatic potential of OS U-2 cells was verified with flow cytometry, trans-well invasion/migration, and western blotting assay. Results: Sorafenib induced the extrinsic and intrinsic apoptotic pathways. In addition, sorafenib reduced the invasion and migration ability of OS cells, induced NF-ĸB activation, and the expression of anti-apoptotic proteins and metastasis-associated proteins encoded by NF-ĸB target genes. Conclusion: Sorafenib led to stimulation of extrinsic/intrinsic apoptotic pathways and NF-ĸB inactivation in U-2 OS cells.