Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway Activation and Epithelial-Mesenchymal Transition In Vivo
Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway Activation and Epithelial-Mesenchymal Transition In Vivo
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姜黄素对烟草烟雾诱导的体内肝脏 MAPK 通路激活和上皮间质转化的影响
DOI：
10.1002/ptr.5844
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发表时间：
2017-08-01
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
吸烟是肝癌的主要危险因素。烟草烟雾诱导的上皮-间质转化（EMT）在癌症的发生和发展中起着至关重要的作用。丝裂原活化蛋白激酶（MAPK）通路在烟草烟雾相关的致癌过程中发挥重要作用，包括EMT过程。补充姜黄素对癌症的化学预防作用已有报道。在本研究中，我们研究了烟草烟雾对MAPK通路激活和EMT改变的影响，并在BALB/c小鼠肝脏中检测了姜黄素的预防作用。我们的研究结果表明，小鼠暴露于烟草烟雾12周后，肝脏组织中ERK1/2、JNK、p38和ERK5通路以及激活蛋白1 （AP-1）蛋白被激活。烟草烟雾使小鼠肝脏上皮标志物mRNA和蛋白表达降低，而肝脏间充质标志物mRNA和蛋白表达升高。姜黄素治疗可有效减弱烟草烟雾诱导的小鼠肝脏ERK1/2和JNK MAPK通路、AP-1蛋白和EMT的激活。我们的数据提示姜黄素对烟草烟雾引发的BALB/c小鼠肝脏MAPK通路激活和EMT的保护作用，从而为烟草烟雾相关肝癌的化学预防提供新的见解。版权所有：John Wiley & Sons， Ltd。
Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright (C) 2017 John Wiley & Sons, Ltd.