title: Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.
abstract: Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin.
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Jia
authors.affiliation: College of Life Science, Shandong Normal University, Jinan, China.
authors.forename: Haiji
authors.initials: H
authors.lastname: Sun
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Hongqiao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Dongjie
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin