Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo

The multikinase-inhibition action of sorafenib provides strong rationales for its combination use with radiotherapy. We investigated the in vitro and in vivo effect of sorafenib combined with irradiation on hepatocellular carcinoma (HCC). Sorafenib enhanced radiosensitivity of human HCC cell lines in a schedule-dependent manner. Sorafenib selectively inhibited radiation-induced activation of vascular endothelial growth factor receptor-2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and suppressed DNA repair capacity, decreased radiation-activated NF-κB and increased radiation-induced apoptosis. In xenograft experiments, combination treatment produced marked tumor growth delay in both concurrent and sequential schedules. These results suggest that sorafenib could potentiate irradiation effect in HCC, which warrants further investigation for its potential clinical applications.

► Sorafenib could potentiate irradiation effect in two HCC cells and their xenografts.
► Inhibition of radiation-induced proliferation and DNA repair capacity by sorafenib may be underlying mechanisms for synergy.
► Promotion of radiation-induced apoptosis by sorafenib may also contribute to the potential effect of irradiation and sorafenib.