STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α

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• 作者：Chi Zhang (1)
  Xi Yang (1)
  Qu Zhang (2)
  Qing Guo (3)
  Jia He (4)
  Qin Qin (1)
  Hongcheng Zhu (1)
  Jia Liu (1)
  Liangliang Zhan (1)
  Jing Lu (1)
  Zheming Liu (1)
  Liping Xu (1)
  Jianxin Ma (2)
  Shengbin Dai (3)
  Hongyan Cheng (1)
  Xinchen Sun (1)
  
• 关键词：Esophageal squamous cell carcinoma ; NSC74859 ; STAT3 ; HIF ; 1α ; Radiotherapy
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：October 2014
• 年：2014
• 卷：35
• 期：10
• 页码：9793-9799
• 全文大小：2,814 KB
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• 作者单位：Chi Zhang (1)
  Xi Yang (1)
  Qu Zhang (2)
  Qing Guo (3)
  Jia He (4)
  Qin Qin (1)
  Hongcheng Zhu (1)
  Jia Liu (1)
  Liangliang Zhan (1)
  Jing Lu (1)
  Zheming Liu (1)
  Liping Xu (1)
  Jianxin Ma (2)
  Shengbin Dai (3)
  Hongyan Cheng (1)
  Xinchen Sun (1)
  
  1. Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
  2. Department of Radiotherapy, Lianyungang Hospital Affiliated to Bengbu Medical College, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, China
  3. Department of Radiotherapy, Taizhou First People’s Hospital, Taizhou, Jiangsu Province, China
  4. Department of Radiotherapy, Jiangyin People’s Hospital, Jiangyin, Jiangsu Province, China
  
• ISSN：1423-0380

文摘

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.