The role of α7-nAChR-mediated PI3K/AKT pathway in lung cancer induced by nicotine.

Nicotine enters the environment mainly through human activity, as well as natural sources. This review article examines the increasing evidence implicating nicotine in the initiation and progression of lung cancer. Moreover, it primarily focuses on elucidating the activation mechanism of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, regulated by α7 subtype nicotinic acetylcholine receptor (α7-nAChR), in relation to the proliferation, invasion, and metastasis of lung cancer cells induced by nicotine, as well as nicotine-mediated anti-apoptotic effects. This process involves PI3K/AKT phosphorylated-B-cell lymphoma-2 (Bcl-2) family proteins, PI3K/AKT/mammalian target of rapamycin (mTOR), PI3K/AKT/nuclear factor-κB (NF-κB), hepatocyte growth factor (HGF)/cellular-mesenchymal epithelial transition factor (c-Met)-induced PI3K/AKT and PI3K/AKT activated-hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathways. In addition, we also deliberated on the related challenges and upcoming prospects within this field. These lay the foundation for further study on nicotine, lung tumorigenesis, and PI3K/AKT related molecular mechanisms. This work has the potential to significantly contribute to the treatment and prognosis of gastric cancer in smokers. Besides, the crucial significance of PI3K/AKT signaling pathway in multiple molecular pathways also suggests that its target antagonists may inhibit the development and progression of lung cancer, providing a possible new perspective for solving the problem of nicotine-promoted lung cancer. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the environmental assessment of tobacco and other nicotine-containing products.