title: Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment.
abstract: 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)-1α and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF-1α and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213001, P.R. China.
authors.forename: Yu-Qiong
authors.initials: YQ
authors.lastname: Ding
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hong-Cheng
authors.initials: HC
authors.lastname: Zhu
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213001, P.R. China.
authors.forename: Ju-Dong
authors.initials: JD
authors.lastname: Luo
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213001, P.R. China.
authors.forename: Xi-Fa
authors.initials: XF
authors.lastname: Zhou
keywords: HIF-1α; esophageal cancer; hypoxia; radiosensitization; sunitinib