Angiotensin II Type 2 Receptor: A Novel Modulator of Inflammation in Pancreatic Ductal Adenocarcinoma through Regulation of NF-ΚB Activity

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Ankit V. Gandhi
Galina `Chipitsyna
Daniel Relles
Charles J. Yeo
Hwyda A. Arafat

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.                                                                                                                                                               

 

Keywords:
Pancreatic Ductal Adenocarcinoma (PDAC), AngII, AT2R, inflammation, NF-κB

Article Details

How to Cite
V. Gandhi, A., `ChipitsynaG., Relles, D., J. Yeo, C., & A. Arafat, H. (2017). Angiotensin II Type 2 Receptor: A Novel Modulator of Inflammation in Pancreatic Ductal Adenocarcinoma through Regulation of NF-ΚB Activity. Journal of Cancer and Tumor International, 5(1), 1-11. https://doi.org/10.9734/JCTI/2017/31326
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Original Research Article