Abstract A38: Adiponectin receptor agonists cause inhibition of pancreatic cancer proliferation

Abstract

Abstract Adiponectin is an anti-atherogenic hormone which is typically decreased in the setting of obesity, diabetes, and pancreatitis. Adiponectin and/or its receptor levels have been inversely correlated with risk for pancreatic cancer. The purpose of this study was to determine the effect of adiponectin on pancreatic cancer cells and to investigate the primary molecular pathways that it regulates. We have previously shown that pancreatic cancer cells primarily produce adiponectin receptor 1. In our current studies, recombinant adiponectin and a novel small molecular adiponectin agonist, AdipoRon, were used to stimulate human and murine pancreatic cancer cell lines in vitro. Proliferation was assessed through an EdU incorporation assay, metabolism was measured through MTT, and apoptosis was assessed through Annexin V staining. Results demonstrate that adiponectin stimulation leads to a decrease in proliferation of pancreatic cancer cells. Further, AdipoRon elicits a more potent suppression of proliferation and an additional increase in apoptosis. To better understand the molecular mechanisms activated by adiponectin stimulation, we performed western blot analysis of treated cells. We were able to confirm that AMPK was a direct target of both adiponectin and AdipoRon. Further, we were able to show that FBS stimulated phosphorylation of Akt was diminished in the presence of AdipoRon. Our data demonstrate that adiponectin and adiponectin receptor agonists act in a suppressive manner against pancreatic cancer cell proliferation. Current studies will determine whether adiponectin agonists can additionally decrease proliferation in vivo. Citation Format: Alisha Mendonsa, Lee Gorden, Michael Nathan VanSaun. Adiponectin receptor agonists cause inhibition of pancreatic cancer proliferation. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A38.