Angiotensin II Type 2 Receptor: A Novel Modulator of Inflammation in Pancreatic Ductal Adenocarcinoma through Regulation of NF-ΚB Activity
Journal Title: Journal of Cancer and Tumor International - Year 2017, Vol 5, Issue 1
Abstract
Aims: The aim of this study was to explore potential pro-inflammatory, pro-migratory and pro-invasive roles of angiotensin II type 2 receptor (AT2R) in pancreatic ductal adenocarcinoma (PDAC) cells. Study Design: AT2R-specific agonist (CGP42112A, CGP), blocking antibody, or siRNA were interchangeably used to analyze functional impact of AT2R on PDAC cell proliferation, migration, and invasion. Results: This study revealed that AT2R blockade reduced proliferation, migration and invasion of PDAC cells. Blocking AT2R significantly lowed the expression of oxidative-stress genes Nox1, Nox3, Nox4, and Nox5, and pro-invasive genes MMP-2, MMP-9, OPN, and α5-integrin. AT2R siRNA significantly downregulated the expression levels of pro-inflammatory IL-1beta, IFN-γ, iNOS, IL-6, IL-8, and IL-15 mRNA. Blocking AT2R also inhibited the intrinsic and angiotensin II (AngII) or CGP-mediated activation of NF-κB. Conclusion: These findings demonstrate previously unknown pro-inflammatory, pro-migratory and pro-invasive effects of AT2R in PDAC cells. Our data suggest that one mechanism by which AT2R promote inflammation is through activation of constitutive and AngII-mediated NF-κB. Thus, AT2R blockade could be a novel therapeutic strategy to target multiple pathways that mediate PDAC carcinogenesis.
Authors and Affiliations
Ankit V. Gandhi, Galina Chipitsyna, Daniel Relles, Charles J. Yeo, Hwyda A. Arafat
Keywords
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- EP ID EP308889
- DOI 10.9734/JCTI/2017/31326
- Views 90
- Downloads 0
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