Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3

Journal of Translational Medicine

Research

Mu-Yan Cai¹  Meng-Zhong Liu²  Qiao-Qiao Li²  Li-Ru He²  Zi-Zhen Feng²  Lei Zhao²  Mian Xi²  Dan Xie³  Yi-Xin Zeng³  Yi-Ji Liao³  Dong Qian³  Jing-Xian Shen⁴ 

[1] Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No 651 Dongfeng Road East, 510060, Guangzhou, China;Departments of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No 651 Dongfeng Road East, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Road East, 510060, Guangzhou, China;Medical Imaging and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, China;

关键词: EGFR;    Esophageal squamous carcinoma cell;    IGFBP-3;    Nimotuzumab;    Radiosensitivity;   

DOI  :  10.1186/1479-5876-10-249

 received in 2012-09-19, accepted in 2012-12-07,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEpidermal growth factor receptor (EGFR) is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC). The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody) on ESCC radiotherapy (RT) and underlying mechanisms.MethodsNimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model.ResultsNimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression) in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR) induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (P<0.05), and even after the administration of Nimotuzumab, the RT response of IGFBP-3 silenced KYSE30 cells was not enhanced (P>0.05). In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029), and also with IGFBP-3 up-regulation in tumor tissue.ConclusionsNimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.

【 授权许可】

Unknown   
© Zhao et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.