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Open Access 01-12-2012 | Research

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

Authors: Lei Zhao, Li-Ru He, Mian Xi, Mu-Yan Cai, Jing-Xian Shen, Qiao-Qiao Li, Yi-Ji Liao, Dong Qian, Zi-Zhen Feng, Yi-Xin Zeng, Dan Xie, Meng-Zhong Liu

Published in: Journal of Translational Medicine | Issue 1/2012

Abstract

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.

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Title: Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3
Authors: Lei Zhao
Li-Ru He
Mian Xi
Mu-Yan Cai
Jing-Xian Shen
Qiao-Qiao Li
Yi-Ji Liao
Dong Qian
Zi-Zhen Feng
Yi-Xin Zeng
Dan Xie
Meng-Zhong Liu
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-10-249

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