Synergistic effect of sorafenib with ionizing radiation on human oral cancer cells

Abstract

Background/aim: Although anticancer effects of sorafenib on renal, liver and colon carcinomas are well-known, its combination effect with ionizing radiation on oral squamous cell carcinoma (OSCC) is unclear. Herein human SAS cells, an OSCC cell line, were used in order to elucidate this combination effect.

Materials and methods: Both SAS and SAS/nuclear factor kappa-B-luciferase (SAS/NF-κB-luc2) cell lines were used in the study. Cell viability, NF-κB activation, and protein expression of NF-κB downstream effectors were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, NF-κB-luc2 reporter gene system, NF-κB/DNA binding activity and western blotting.

Results: Sorafenib significantly increased radiation-induced cytotoxicity and apoptosis via both mitochondrial-dependent and independent pathways. In addition, NF-κB activity and downstream effector protein expression induced by radiation was suppressed by sorafenib in SAS/NF-κB-luc2 cells.

Conclusion: Combination of sorafenib with radiation for the treatment of human OSCC shows a synergistic effect via suppression of radiation-induced NF-κB activity and its regulated downstream effector proteins.

Keywords: NF-κB; Sorafenib; human oral squamous cell carcinoma; radiation.