In this study, we investigated a molecular mechanism underlying VEGF signaling by nicotine in two NSCLC cell lines, A549 (p53 wild-type) and H1299 (p53-null), and show that the nicotine treatment of NSCLC cells leads to increased levels of adrenaline, noradrenaline, VEGF, and activities of PI3K, AKT, NFκB, and also to decreased GABA levels and p53 activity via a mechanism involving α7nAChR, α4β2nAChR, and β-ARs, leading to cell survival. This evidence concerns the gene AKT1 and non-small cell lung carcinoma.