Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3.
Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3.
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Nimotuzumab 通过上调 IGFBP-3 促进 EGFR 过表达食管鳞状细胞癌细胞的放射敏感性。
DOI：
10.1186/1479-5876-10-249
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发表时间：
2012-12-11
影响因子：
7.4
通讯作者：
Liu MZ
中科院分区：
文献类型：
--
作者：
Zhao L;He LR;Xi M;Cai MY;Shen JX;Li QQ;Liao YJ;Qian D;Feng ZZ;Zeng YX;Xie D;Liu MZ
表皮生长因子受体（EGFR）被认为可以预测人食管鳞状细胞癌（ESCC）的放射敏感性和/或预后。本研究的目的是研究Nimotuzumab（一种抗egfr单克隆抗体）对ESCC放疗（RT）的疗效及其机制。将尼莫妥珠单抗给予2株经rt处理的ESCC细胞株KYSE30和TE-1，观察细胞生长、集落形成和凋亡情况。采用RNA干扰法研究胰岛素样生长因子结合蛋白-3 （IGFBP-3）在尼莫单抗治疗ESCC细胞放射敏感性中的作用。采用小鼠异种移植模型研究尼妥珠单抗对ESCC放疗的体内影响。Nimotuzumab增强KYSE30细胞（EGFR高表达）在体外的辐射应答，这可以通过增加辐射抑制的细胞生长和集落形成以及辐射介导的凋亡来证明。机制研究显示，尼妥珠单抗抑制KYSE30细胞中EGF诱导的磷酸化EGFR （p-EGFR）。此外，短发卡RNA敲除IGFBP-3显著降低KYSE30细胞的放射敏感性（P<0.05），并且即使在给予尼莫单抗后，IGFBP-3沉默的KYSE30细胞的RT反应也没有增强（P<0.05）。在KYSE30细胞异种移植物中，与单独放疗相比，尼妥珠单抗联合放疗导致肿瘤生长明显延迟（P=0.029），并且肿瘤组织中IGFBP-3上调。尼莫单抗可增强EGFR通路具有功能性活性的ESCC细胞的RT效应。特别是，尼莫单抗增加ESCC放射敏感性可能依赖于通过egfr依赖途径上调IGFBP-3。
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. 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. 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. 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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DOI：
10.1152/ajpgi.00344.2005
发表时间：
2006-02-01
影响因子：
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作者：
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