Lack of chemopreventive effects of P2X7R inhibitors against pancreatic cancer.

ABSTRACT: Pancreatic cancer (PC) is an almost uniformly lethal disease with inflammation playing an important role in its progression. Sustained stimulation of purinergic receptor P2X7 drives induction of NLRP inflammasome activation. To understand the role of P2X7 receptor and inflammasome, we performed transcriptomic analysis of p48^Cre/+-LSL-Kras^G12D/+ mice pancreatic tumors by next generation sequencing. Results showed that P2X7R's key inflammasome components, IL-1β and caspase-1 are highly expressed (p < 0.05) in pancreatic tumors. Hence, to target P2X7R, we tested effects of two P2X7R antagonists, A438079 and AZ10606120, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PC in p48^Cre/+-LSL-Kras^G12D/+ mice. Following dose

SUBMITTER: Mohammed A 

PROVIDER: S-EPMC5716694 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature