Nicotine suppresses apoptosis by regulating ?7nAChR/Prx1 axis in oral precancerous lesions.

ABSTRACT: 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, ?3nAChR, ?7nAChR, 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 ?7nAChR activated apoptosis, and nicotine increased the expression of Prx1, ?3nAChR and ?7nAChR, and inhibited MAPK activation. Moreover, nicotine suppressed apoptosis depending on Prx1 and ?7nAChR 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 ?7nAChR/Prx1 during carcinogenesis of OSCC.

SUBMITTER: Wang C 

PROVIDER: S-EPMC5650400 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature