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Nutrients. 2016 Jul 20;8(7). pii: E380. doi: 10.3390/nu8070380.

EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice.

Lu L1, Chen J2, Tang H3, Bai L4, Lu C5, Wang K6, Li M7, Yan Y8, Tang L9, Wu R10, Ye Y11, Jin L12, Liang Z13,14.

Author information

1
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lu_ling60@sina.com.
2
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lengyuing@163.com.
3
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. zjfyeb@163.com.
4
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. bai_ling1234@126.com.
5
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lucn816@163.com.
6
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. m17705286156@163.com.
7
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. limanli123@126.com.
8
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. 18752970933@163.com.
9
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. m17705286167_1@163.com.
10
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. w871647946@163.com.
11
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China. jamesnone@163.com.
12
Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. 13862451566@163.com.
13
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China. liangzhaofeng@ujs.edu.cn.
14
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China. liangzhaofeng@ujs.edu.cn.

Abstract

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.

KEYWORDS:

EGCG; ERK5; epithelial-mesenchymal transition; gastric cancer; tobacco smoke

PMID:
27447666
PMCID:
PMC4963860
DOI:
10.3390/nu8070380
[Indexed for MEDLINE]
Free PMC Article

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