Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium
Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium
复制标题
厄洛替尼促进肠上皮内质网应激介导的损伤
DOI：
10.1016/j.taap.2014.04.015
复制
发表时间：
2014-07-01
影响因子：
3.8
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Fan, Lu;Hu, Lingna;Xu, Qiang
厄洛替尼（Erlotinib）是一种治疗非小细胞肺癌（NSCLC）的常用药物，约55%的患者服用此药后会导致腹泻。在本研究中，我们发现厄洛替尼通过增加上皮通透性和下调E-cadherin来诱导大鼠小肠上皮细胞（IEC-6）屏障功能障碍。厄洛替尼处理后，IEC-6细胞中各种促炎细胞因子（Il-6、Il-25和Il-17f） mRNA水平升高。厄洛替尼浓度和时间依赖性诱导IEC-6和人结肠上皮细胞凋亡和内质网（ER）应激（CCD 841 CoN）。厄洛替尼对雄性C57BL/6J小鼠也有肠上皮损伤。用小干扰RNA敲除C/EBP同源蛋白（CHOP）部分逆转厄洛替尼诱导的肠上皮细胞凋亡、IL-6的产生和E-cadherin的下调。综上所述，厄洛替尼引起肠上皮内质网应激介导的损伤，导致患者腹泻的副作用。(C) 2014爱思唯尔公司版权所有。
Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. (C) 2014 Elsevier Inc. All rights reserved.