EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice.
EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice.
复制标题
EGCG 抑制 ERK5 激活以逆转烟草烟雾引发的 BALB/c 小鼠胃上皮间质转化
DOI：
10.3390/nu8070380
复制
发表时间：
2016-07-20
期刊：
影响因子：
5.9
通讯作者：
Liang Z
中科院分区：
文献类型：
--
作者：
Lu L;Chen J;Tang H;Bai L;Lu C;Wang K;Li M;Yan Y;Tang L;Wu R;Ye Y;Jin L;Liang Z
吸烟是胃癌的重要危险因素。上皮-间质转化是肿瘤发生发展的重要病理生理过程。上皮-间充质转化的ERK 5调节可能对细胞类型和/或细胞微环境敏感，并且其在上皮-间充质转化过程中的作用仍然难以捉摸。表没食子儿茶素没食子酸酯（Epigallocatechin-3-gallate，EGCG）是一种很有前途的癌症化学预防剂。在本研究中，我们研究了ERK 5在烟草烟雾诱导的小鼠胃上皮-间质转化中的调节作用以及EGCG的预防作用。暴露于烟草烟雾12周的小鼠上皮标志物E-cadherin，ZO-1和CK 5的表达减少，而间充质标志物Snail-1，波形蛋白和N-cadherin的表达增加。重要的是，我们证明了ERK 5调节烟草烟雾介导的小鼠胃上皮-间充质转化，如烟草烟雾升高ERK 5活化的发现所证明的，并且烟草烟雾触发的上皮-间充质转化被ERK 5抑制逆转。EGCG（100 mg/kg BW）治疗有效地减弱了烟草烟雾引发的小鼠胃中ERK 5的活化和上皮-间质转化改变。总的来说，这些数据表明，ERK 5是烟草烟雾触发的胃上皮间质转化所必需的，并且EGCG抑制ERK 5活化以逆转烟草烟雾触发的BALB/c小鼠胃上皮间质转化。这些发现为烟草烟雾相关性胃癌的发生机制和化学预防提供了新的见解。
Tobacco smoke is an important risk factor of gastric cancer. Epithelial-mesenchymal transition is a crucial pathophysiological process in cancer development. ERK5 regulation of epithelial-mesenchymal transition may be sensitive to cell types and/or the cellular microenvironment and its role in the epithelial-mesenchymal transition process remain elusive. Epigallocatechin-3-gallate (EGCG) is a promising chemopreventive agent for several types of cancers. In the present study we investigated the regulatory role of ERK5 in tobacco smoke-induced epithelial-mesenchymal transition in the stomach of mice and the preventive effect of EGCG. Exposure of mice to tobacco smoke for 12 weeks reduced expression of epithelial markers E-cadherin, ZO-1, and CK5, while the expression of mesenchymal markers Snail-1, Vimentin, and N-cadherin were increased. Importantly, we demonstrated that ERK5 modulated tobacco smoke-mediated epithelial-mesenchymal transition in mice stomach, as evidenced by the findings that tobacco smoke elevated ERK5 activation, and that tobacco smoke-triggered epithelial-mesenchymal transition was reversed by ERK5 inhibition. Treatment of EGCG (100 mg/kg BW) effectively attenuated tobacco smoke-triggered activation of ERK5 and epithelial-mesenchymal transition alterations in mice stomach. Collectively, these data suggested that ERK5 was required for tobacco smoke-triggered gastric epithelial-mesenchymal transition and that EGCG suppressed ERK5 activation to reverse tobacco smoke-triggered gastric epithelial-mesenchymal transition in BALB/c mice. These findings provide new insights into the mechanism of tobacco smoke-associated gastric tumorigenesis and the chemoprevention of tobacco smoke-associated gastric cancer.