Date Approved
2025
Degree Type
Open Access Thesis
Degree Name
Master of Science (MS)
Department or School
Chemistry
Committee Member
Hedeel Evans, Ph.D., Chair
Committee Member
Brittany Albaugh, Ph.D.
Committee Member
Steven Backues, Ph.D.
Abstract
Nicotine is known to enhance tumor progression in non-small cell lung cancer (NSCLC) by modulating multiple signaling pathways. In this study, we investigated how nicotine influences vascular endothelial growth factor (VEGF) signaling in A549 (p53 wild-type) and H1299 (p53- null) NSCLC cell lines via acetylcholine and β-adrenergic receptor pathways. Nicotine treatment led to increased secretion of epinephrine, norepinephrine, and VEGF; reduced levels of GABA; and activation of PI3K, AKT, and NFκB in both cell lines, while suppressing p53 activity in A549 cells. These effects were reversed by co-treatment with inhibitors targeting α7nAChR, α4β2nAChR, and/or β-ARs. The knockdown of p53 elevated VEGF secretion, and VEGF immunodepletion restored p53 activity. Further, anti-VEGF antibodies blocked nicotine-induced activation of PI3K/AKT/NFκB and restored p53 signaling, leading to reduced cell viability and enhanced apoptosis. Overall, these findings highlight VEGF as a critical mediator downstream of nicotine that integrates cholinergic and adrenergic signaling to regulate NSCLC cell survival.
Recommended Citation
Wozniak, Caroline, "Vascular endothelial growth factor signaling regulation by acetylcholine-and/or β-adrenergic-receptors in human lung cancer cells" (2025). Master's Theses and Doctoral Dissertations. 1354.
https://commons.emich.edu/theses/1354