title: STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α.
abstract: Radiotherapy is the main therapy for inoperable and locally advanced esophageal squamous cell carcinoma (ESCC). However, radioresistance in ESCC remains a challenge. The aim of this study is to investigate the radiosensitizing effects of STAT3 inhibitor NSC74859 on ESCC and explore the underlying mechanisms. ECA109 and TE13 cells were exposed to hypoxia, and treated with NSC74859 or radiation, alone or in combination. Cell proliferation, survival, apoptosis, and double-stranded DNA breaks (DSBs) were examined. Nude mice model of ECA109 xenograft was treated with radiation and/or NSC74859. The levels of STAT3, p-STAT3, HIF-1α, and VEGF were detected by Western blot analysis. NSC74859 efficiently radiosensitized ESCC cells and xenografts in nude mice, and inhibited hypoxia-/radiation-induced activation of STAT3 and upregulation of HIF-1α and VEGF expression. NSC74859 confers radiosensitivity in ESCC via the inhibition of STAT3 activation and the downregulation of HIF-1α and VEGF expression. NSC74859 may become a promising radiosensitizer for ESCC radiotherapy.
authors: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Chi
authors: C
authors: Zhang
authors: Xi
authors: X
authors: Yang
authors: Qu
authors: Q
authors: Zhang
authors: Qing
authors: Q
authors: Guo
authors: Jia
authors: J
authors: He
authors: Qin
authors: Q
authors: Qin
authors: Hongcheng
authors: H
authors: Zhu
authors: Jia
authors: J
authors: Liu
authors: Liangliang
authors: L
authors: Zhan
authors: Jing
authors: J
authors: Lu
authors: Zheming
authors: Z
authors: Liu
authors: Liping
authors: L
authors: Xu
authors: Jianxin
authors: J
authors: Ma
authors: Shengbin
authors: S
authors: Dai
authors: Hongyan
authors: H
authors: Cheng
authors: Xinchen
authors: X
authors: Sun
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000636:Aminosalicylic Acids; D001557:Benzenesulfonates; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C520337:NSC 74859; D011838:Radiation-Sensitizing Agents; D050796:STAT3 Transcription Factor