title: STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma.
abstract: The radioresistance of esophageal squamous cell carcinoma (ESCC) remains an obstacle for the effective radiotherapy of ESCC. This study aimed to investigate the radiosensitization of ESCC by signal transducer and activator of transcription 3 (STAT3) inhibitor stattic. ECA109, TE13, and KYSE150 cell lines were exposed to hypoxia and treated with stattic or radiation, alone or in combination. Cell proliferation, colony formation, apoptosis, and double-stranded DNA breaks (DSBs) were examined. In addition, ECA109 cells were xenografted into nude mice and treated with radiation and/or stattic. The levels of STAT3, p-STAT3, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in ESCC cells and xenografts were detected by Western blot and immunohistochemical analysis. Our results showed that stattic efficiently radiosensitized ESCC cells and xenografts, especially under hypoxia. Moreover, stattic inhibited STAT3 activation and downregulated HIF-1α and VEGF expression. In conclusion, stattic confers radiosensitivity in ESCC cells in vitro and in vivo and is a potential adjuvant for the radiotherapy of ESCC in the clinical setting.
authors.affiliation: Department of Radiotherapy, Hubei Cancer Hospital, Wuhan, China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Desheng
authors.initials: D
authors.lastname: Hu
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Yahui
authors.initials: Y
authors.lastname: Kang
authors.forename: Ruifang
authors.initials: R
authors.lastname: She
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Wang
authors.forename: Defan
authors.initials: D
authors.lastname: Li
authors.forename: Guanhong
authors.initials: G
authors.lastname: Huang
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Ma
authors.forename: Weidong
authors.initials: W
authors.lastname: Mao
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhou
authors.forename: Chuangying
authors.initials: C
authors.lastname: Xiao
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000648:ultrastructure; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003499:Cyclic S-Oxides / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000648:ultrastructure; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D003499:Cyclic S-Oxides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A; C517409:stattic