STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma

• Published in: Tumor biology 2015-03, Vol.36 (3), p.2135-2142
• Main Authors: Zhang, Qu, Zhang, Chi, He, Jia, Guo, Qing, Hu, Desheng, Yang, Xi, Wang, Jinfeng, Kang, Yahui, She, Ruifang, Wang, Zhongming, Li, Defan, Huang, Guanhong, Ma, Zhaoming, Mao, Weidong, Zhou, Xiaoyi, Xiao, Chuangying, Sun, Xinchen, Ma, Jianxin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - ultrastructure; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclic S-Oxides - pharmacology; DNA Breaks, Double-Stranded - drug effects; DNA Breaks, Double-Stranded - radiation effects; Down-Regulation - drug effects; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - ultrastructure; Esophageal Squamous Cell Carcinoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pharmacology; Protein expression; Radiation therapy; Radiation Tolerance - drug effects; Research Article; Signal transduction; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2823-y

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.