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

Journal of Translational Medicine

Meng-Zhong Liu¹  Dan Xie¹  Yi-Xin Zeng¹  Zi-Zhen Feng¹  Dong Qian¹  Yi-Ji Liao¹  Qiao-Qiao Li¹  Jing-Xian Shen²  Mu-Yan Cai³  Mian Xi¹  Li-Ru He¹  Lei Zhao¹ 

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

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

Others  :  828360
DOI  :  10.1186/1479-5876-10-249

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

【 摘 要 】

Background

Epidermal 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.

Methods

Nimotuzumab 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.

Results

Nimotuzumab 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.

Conclusions

Nimotuzumab 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】

   
2012 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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