Norepinephrine Bitartrate for Genotype-Dependent Adrenergic Signaling Analysis in Pancreatic Ductal Adenocarcinoma
Brak HH, et al. Advances in Biological Regulation, 2025, 97, 101097.
Norepinephrine bitartrate was applied as a defined adrenergic agonist to investigate genotype-dependent signaling mechanisms in human pancreatic ductal adenocarcinoma (PDAC) cell lines. In vitro proliferation and migration were quantified following treatment with graded concentrations of norepinephrine bitartrate, with and without selective α1- and β-adrenergic receptor antagonists. Wound-healing assays were conducted to assess migratory capacity, while RT-qPCR was employed to quantify transcriptional modulation of adrenergic receptors and KRAS downstream effectors. Protein expression levels of MMP-9, VIM, CCND1, mTOR, and RhoA were further analyzed to delineate oncogenic pathway alterations. Experimental results demonstrated genotype-specific responses, including enhanced proliferation and migration mediated predominantly through β2-adrenergic signaling, alongside α1-dependent negative feedback regulation of receptor expression. Notably, norepinephrine bitartrate significantly reduced MMP-9 expression, an effect reversible by adrenergic antagonism, confirming its utility as a precise pharmacological tool for dissecting adrenergic-KRAS signaling crosstalk in PDAC.