Blockade of α7 nicotinic acetylcholine receptors inhibit nicotine-induced tumor growth and vimentin expression in non-small cell lung cancer through MEK/ERK signaling way

Zhang,Chun; Yu,Ping; Zhu,Liang; Zhao,Qingnan; Lu,Xiaotong; Bo,Shuhong

doi:10.3892/or.2017.6014

Blockade of α7 nicotinic acetylcholine receptors inhibit nicotine-induced tumor growth and vimentin expression in non-small cell lung cancer through MEK/ERK signaling way

Authors:
- Chun Zhang
- Ping Yu
- Liang Zhu
- Qingnan Zhao
- Xiaotong Lu
- Shuhong Bo
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Affiliations: Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
Published online on: October 2, 2017 https://doi.org/10.3892/or.2017.6014
Pages: 3309-3318
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nicotine can stimulate the progression of non-small cell lung cancer (NSCLC) through nicotinic acetylcholine receptors (nAChRs). The persistent proliferation of cancer cells is one of the key effects of nicotinic signaling. The present study aimed to clarify the mechanism of nicotine-induced proliferation in NSCLCs at the receptor subtype level. We have previously reported that there are various subtypes of nicotinic receptors expressed in NSCLC cell lines. In the present study, we demonstrated that blocking α7nAChRs agonized by nicotine could suppress the proliferation of H1299 cells in vitro and decrease H1299 tumor xenograft growth in nude mice. During this process, the expression of vimentin was also markedly attenuated, concomitant with the decreased expression of α7nAChR. These results were ascertained by knocking down the α7nAChR gene to abolish receptor functioning. Furthermore, under the stimulation of nicotine, the MEK/ERK signaling pathway was found to be inhibited when cells were treated with an antagonist of α7nAChR or an inhibitor of MEK. Collectively the results indicate that the changes in proliferation and vimentin expression of H1299 cells in response to α7nAChR stimulation are mediated by the MEK/ERK pathway. These findings demonstrate that α7nAChR plays an important role in H1299 cell proliferation, tumor growth and expression of vimentin. Therefore, blocking α7nAChRs in NSCLC may be a potential adjuvant therapy for the targeted treatment of NSCLC.

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