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The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin

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Tumor Biology

Abstract

Nimotuzumab is an antibody against epidermal growth factor receptor (EGFR). The objective of this study was to examine the capacity and specific underlying mechanisms of nimotuzumab to modulate cytotoxicity of cisplatin (DDP) in esophageal squamous cell carcinoma (ESCC) cell lines with different EGFR expression levels. Nimotuzumab was administrated to two ESCC cell lines KYSE30 and TE-1 treated with DDP. Cell growth, colony formation, and apoptosis were analyzed by MTT and flow cytometry assays. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells chemosensitivity treated with nimotuzumab. Combination of nimotuzumab and DDP resulted in a DDP cytotoxicity increase in overexpressing EGFR cells (KYSE30) but not in low-expressing EGFR cells (TE-1). Meantime, DDP activated the EGFR pathway in the two cell lines in a ligand-independent fashion. Furthermore, DDP-induced EGFR activation was inhibited by nimotuzumab in KYSE30 cells, and this result was not observed in TE-1 cells. EGF reduced the expression of IGFBP-3 in KYSE30 cells; however, nimotuzumab could reverse the downregulation of IGFBP-3, and this result was also not observed in TE-1 cells. After IGFBP-3 was silenced by small interfering RNA, the potential of nimotuzumab to enhance DDP-mediated cytotoxicity was inhibited in KYSE30 cells. The results indicated that the increased ESCC chemosensitivity to DDP by nimotuzumab might be dependent on IGFBP-3 upregulation through EGFR-dependent pathway, which would facilitate preselection of ESCC patients for treatment of nimotuzumab combined with DDP.

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Acknowledgments

This work was supported by grants from the Major State Basic Research Program (973 project) of China (2010CB912802 and 2010CB529401).

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Authors and Affiliations

  1. Department of Radiotherapy, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou, 510060, China

    Lei Zhao, Qiao-Qiao Li, Rui Zhang, Mian Xi, Li-Ru He & Meng-Zhong Liu

  2. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China

    Lei Zhao, Qiao-Qiao Li, Rui Zhang, Mian Xi, Yi-Ji Liao, Dong Qian, Li-Ru He, Yi-Xin Zeng, Dan Xie & Meng-Zhong Liu

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  1. Lei Zhao
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  2. Qiao-Qiao Li
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Correspondence to Meng-Zhong Liu.

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Lei Zhao and Qiao-Qiao Li contributed equally to this work.

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Zhao, L., Li, QQ., Zhang, R. et al. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumor Biol. 33, 1115–1123 (2012). https://doi.org/10.1007/s13277-012-0352-0

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  • DOI: https://doi.org/10.1007/s13277-012-0352-0

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