Abstract 1127 Analysis of Gene Networks of KLF4 and NR4A1 in Apoptosis, Epithelial Mesenchymal Transition/Cancer Stemness, and DNA Damage Response in Ovarian Cancer

Nicotine is known to regulate both b-adrenergic receptors (b-ARs) and nicotinic acetylcholine receptors (nAChRs), promoting oncogenic signaling.Using non-small cell lung cancer (NSCLC) cell lines A549 and H1299, we demonstrate that nicotine exposure increases adrenaline/noradrenaline and VEGF levels, along with PI3K/AKT pathway activity.A549 cells treated with nicotine and adrenaline/noradrenaline showed decreased p53 activity, which increased with GABA incubation.Moreover, VEGF levels in A549 media increased upon p53 knockdown.Treatment with anti-VEGF antibodies decreased cell viability, enhanced apoptosis, inhibited PI3K, AKT, and NFkB activity, and led to increased p53 activation in A549 cells.Methods include Western blotting, kinetics, ELI-SAs to measure p53, VEGF, PI3K, NFkB and AKT activity, siRNA transfections, MTT assays to assess cell viability, and caspase-3 assays to quantify apoptosis.In summary, VEGF is downregulated via GABA and/or p53 and upregulated through