Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke-induced Gastric Epithelial-Mesenchymal Transition in Mice
Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke-induced Gastric Epithelial-Mesenchymal Transition in Mice
复制标题
姜黄素抑制 MAPK 通路逆转烟草烟雾诱导的小鼠胃上皮间质转化
DOI：
10.1002/ptr.5398
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发表时间：
2015-10-01
影响因子：
7.2
通讯作者：
Han, Hongyu
中科院分区：
文献类型：
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作者：
Liang, Zhaofeng;Wu, Rui;Han, Hongyu
烟草烟雾（TS）已被证明会导致胃癌。上皮-间质转化（Epithelial-mesenchymal transition， EMT）是肿瘤发生的重要病理生理过程。丝裂原活化蛋白激酶（MAPK）通路在肿瘤发生包括EMT过程中起核心作用。姜黄素是一种很有前途的化学预防剂，可以预防多种癌症。在本研究中，我们研究了TS对小鼠胃MAPK通路激活和EMT改变的影响，并进一步研究了姜黄素的预防作用。结果显示，小鼠暴露于TS 12周后，胃细胞外调节蛋白激酶1和2 （ERK1/2）、Jun n末端激酶（JNK）、p38和ERK5 MAPK通路以及激活蛋白1 （AP-1）蛋白被激活。TS降低了上皮标记物E-cadherin和ZO-1的mRNA和蛋白表达水平，升高了间质标记物vimentin和N-cadherin的mRNA和蛋白表达水平。姜黄素治疗有效地消除了ts触发的ERK1/2和JNK MAPK通路、AP-1蛋白和EMT改变的胃激活。这些结果首次提示了姜黄素在长期TS暴露诱导的胃MAPK激活和EMT中的保护作用，从而为TS相关胃癌的发病机制和化学预防提供了新的见解。版权所有：John Wiley & Sons， Ltd
Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen-activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N-terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP-1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E-cadherin and ZO-1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N-cadherin were increased. Treatment of curcumin effectively abrogated TS-triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long-term TS exposure-induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS-associated gastric cancer. Copyright (c) 2015 John Wiley & Sons, Ltd.