Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3
| Autor: | Mian Xi, Jing Xian Shen, Meng Zhong Liu, Yi Ji Liao, Qiao Qiao Li, Mu Yan Cai, Li Ru He, Zizhen Feng, Lei Zhao, Dong Qian, Yi Xin Zeng, Dan Xie |
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| Rok vydání: | 2012 |
| Předmět: |
Oncology
medicine.medical_specialty Esophageal Neoplasms medicine.drug_class EGFR Blotting Western lcsh:Medicine Apoptosis Biology Antibodies Monoclonal Humanized Monoclonal antibody Radiation Tolerance General Biochemistry Genetics and Molecular Biology Radiosensitivity Cell Line Tumor Internal medicine Carcinoma medicine Humans Nimotuzumab Epidermal growth factor receptor Medicine(all) Biochemistry Genetics and Molecular Biology(all) Research lcsh:R IGFBP-3 General Medicine Esophageal squamous carcinoma cell medicine.disease Immunohistochemistry Up-Regulation ErbB Receptors Insulin-Like Growth Factor Binding Protein 3 Monoclonal Carcinoma Squamous Cell Cancer research biology.protein Antibody medicine.drug |
| Zdroj: | Journal of Translational Medicine Journal of Translational Medicine, Vol 10, Iss 1, p 249 (2012) |
| ISSN: | 1479-5876 |
| Popis: | 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 (PP>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. |
| Databáze: | OpenAIRE |
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