Volume 29, Issue 10 pp. 1665-1671
Research Article

Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke-induced Gastric Epithelial–Mesenchymal Transition in Mice

Zhaofeng Liang

Zhaofeng Liang

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Rui Wu

Rui Wu

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Wei Xie

Wei Xie

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Hao Geng

Hao Geng

Department of Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, 230032 China

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Li Zhao

Li Zhao

Department of Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, 230032 China

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Chunfeng Xie

Chunfeng Xie

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Jieshu Wu

Jieshu Wu

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Shanshan Geng

Shanshan Geng

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Xiaoting Li

Xiaoting Li

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Mingming Zhu

Mingming Zhu

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Weiwei Zhu

Weiwei Zhu

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Jianyun Zhu

Jianyun Zhu

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Cong Huang

Cong Huang

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Xiao Ma

Xiao Ma

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

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Caiyun Zhong

Corresponding Author

Caiyun Zhong

Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

Correspondence to: Caiyun Zhong, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, 818 East Tianyuan Rd, Jiangning, Nanjing 211166, China; Hongyu Han, Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

E-mail: [email protected] (Caiyun Zhong); [email protected] (Hongyu Han)

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Hongyu Han

Corresponding Author

Hongyu Han

Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060 China

Correspondence to: Caiyun Zhong, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, 818 East Tianyuan Rd, Jiangning, Nanjing 211166, China; Hongyu Han, Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

E-mail: [email protected] (Caiyun Zhong); [email protected] (Hongyu Han)

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First published: 14 June 2015
Citations: 28

Abstract

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 12 weeks 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 © 2015 John Wiley & Sons, Ltd.

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