Nicotine suppresses apoptosis by regulating α7nAChR/Prx1 axis in oral precancerous lesions
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Chunxiao Wang1, Wenwen Niu1, Hui Chen1, Ni Shi2, Dian He3, Min Zhang1, Lihua Ge1, Zhenchuan Tian1, Moci Qi1, Tong Chen2,* and Xiaofei Tang1,*
1Division of Oral Pathology, Beijing Institute of Dental Research, Beijing Key laboratory, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Dongcheng District, Beijing, China
2Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA
3Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
*These authors have contributed equally to this work
Xiaofei Tang, email: email@example.com
Tong Chen, email: firstname.lastname@example.org
Keywords: oral precancerous lesion, Prx1, nicotine, α3nAChR, α7nAChR
Received: February 22, 2017 Accepted: July 29, 2017 Published: August 24, 2017
Nicotine, a tumor promoter in tobacco, can increase Peroxiredoxin (Prx1) and nicotinic acetylcholine receptors (nAChRs) in oral squamous cell carcinoma (OSCC). In the present study, we investigate the effects of nicotine in oral precancerous lesions focusing on apoptosis and nAChR/Prx1 signaling. We detected expression of Prx1, α3nAChR, α7nAChR, phosphorylation of mitogen-activated protein kinases (MAPK) and apoptosis in dysplastic oral keratinocyte (DOK) cells as well as in 4-nitroquinoline 1-oxide (4NQO) or 4NQO + nicotine – induced oral precancerous lesions in Prx1 wild-type (Prx1+/+) and Prx1 knockdown (Prx1+/-) mice. In DOK cells, Prx1 knockdown and blocking α7nAChR activated apoptosis, and nicotine increased the expression of Prx1, α3nAChR and α7nAChR, and inhibited MAPK activation. Moreover, nicotine suppressed apoptosis depending on Prx1 and α7nAChR in DOK cells. In animal bioassay, nicotine and Prx1 promoted growth of 4NQO-induced precancerous lesions in mouse tongue. 4NQO plus nicotine suppressed MAPK activation in Prx1 wild-type mice but not in Prx1 knockdown mice. Our data demonstrate that nicotine inhibits cell apoptosis and promotes the growth of oral precancerous lesions via regulating α7nAChR/Prx1 during carcinogenesis of OSCC.
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