Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment.

Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation. Sunitinib potently inhibited ESCC cell proliferation in an MTT assay. In a clonogenic survival assay, sunitinib sensitized hypoxic ESCC cells to radiation, with sensitizing enhancement ratios of 1.31-1.59. In addition, sunitinib promoted the apoptosis of ESCC cells, but did not alter their cell cycle distribution. Radiosensitization was accompanied by inhibition of the radiation-induced upregulation of hypoxia-inducible factor (HIF)-1 alpha and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF-1 alpha and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.