Curcumin reverses tobacco smoke‑induced epithelial‑mesenchymal transition by suppressing the MAPK pathway in the lungs of mice

Liang,Zhaofeng; Wu,Rui; Xie,Wei; Zhu,Mingming; Xie,Chunfeng; Li,Xiaoting; Zhu,Jianyun; Zhu,Weiwei; Wu,Jieshu; Geng,Shanshan; Xu,Wenrong; Zhong,Caiyun; Han,Hongyu

doi:10.3892/mmr.2017.8028

Curcumin reverses tobacco smoke‑induced epithelial‑mesenchymal transition by suppressing the MAPK pathway in the lungs of mice

Authors:
- Zhaofeng Liang
- Rui Wu
- Wei Xie
- Mingming Zhu
- Chunfeng Xie
- Xiaoting Li
- Jianyun Zhu
- Weiwei Zhu
- Jieshu Wu
- Shanshan Geng
- Wenrong Xu
- Caiyun Zhong
- Hongyu Han
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Affiliations: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, Department of Clinical Nutrition, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
Published online on: November 13, 2017 https://doi.org/10.3892/mmr.2017.8028
Pages: 2019-2025

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Abstract

Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin. The protein expression levels analyzed by western blot analysis demonstrated that 12 weeks of tobacco smoke exposure activated extracellular‑signal‑regulated kinase (ERK) 1/2, c‑Jun N‑terminal kinase (JNK) and p38 MAPK pathways, in addition to AP‑1, in the lungs of mice, while reducing the activation of ERK5/MAPK pathways. The results also indicated that the mRNA and protein levels of the epithelial markers E‑cadherin and zona occludens‑1 were reduced following tobacco smoke exposure. Conversely, the expression levels of mRNA and protein for the mesenchymal markers vimentin and N‑cadherin were increased. Curcumin treatment inhibited tobacco smoke‑induced MAPK/AP‑1 activation, including ERK1/2, JNK and p38 MAPK pathways, and AP‑1 proteins, and reversed EMT alterations in lung tissue. The results of the present study provide new insights into the molecular mechanisms of tobacco smoke‑associated lung cancer and may open up new avenues in the search for potential therapeutic targets in lung tumorigenesis.

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