期刊
FRONTIERS IN PHARMACOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2017.00573
关键词
alpha5 nicotinic acetylcholine receptor; cell cycle; tumor growth; survival time; nicotine; non-small cell lung cancer
资金
- National Natural Science Foundation of China [81272588, 81602593, 31672286]
- Natural Science Foundation of Shandong Provincial, China [ZR2012HM061]
Nicotine and nicotinic acetylcholine receptors (nAChRs) are considered to be involved in lung cancer risk, onset and progression, but their precise physiological roles in these contexts remain unclear. Our previous studies suggested that alpha 5-nAChR mediates nicotine-induced lung cancer cell proliferation, migration, and invasion in vitro. In this study, we aimed to determine the role of a alpha 5-nAChR in the development and progression of non-small cell lung cancer (NSCLC). Our microarray results reveal that knockdown of the CHRNA5 gene encoding a alpha 5-nAChR significantly modulates key pathways including the cell cycle, DNA replication, pathway in cancer. a alpha 5-nAChR knockdown in cultured A549 cells affected cell cycle distribution, apoptosis, and cyclin expression. In vivo, a alpha 5-nAChR silencing inhibited the growth of lung tumors, especially in the context of nicotine exposure. Importantly, alpha 5-nAChR expression in patient tumors correlated with the primary T stage, N stage, and reduced survival time. These results reveal that alpha 5-nAChR silencing inhibits the progression of nicotine-related NSCLC, making this receptor a potential pharmacological target for the treatment of nicotine-related lung carcinogenesis.
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