AMPK-SIRT1 Pathway Modulates The Apoptosis, Proliferation and Migration of AR42J Cells By Regulating p53 and NF-κB

Abstract

Background: Acute pancreatitis (AP) is an acute abdomen caused by abnormal activation of trypsin. AMPK-SIRT1 pathway has been reported to be related to various diseases, but the function in AP remains unclear. This study is designed to investigate the mechanism and effect of AMPK-SIRT1 pathway in AP.Methods: An experimental AP model of AR42J cells was stimulated with caerulein after pretreated with compound C or metformin. The mRNA and protein expressions of genes were analyzed by qRT-PCR and western blot. Cell apoptosis, proliferation and migration were measured using flow cytometry, MTT and transwell assay. Results: After pretreated with metformin, expressions of p-AMPKα, SIRT1 were elevated, ace-p53, ace-NF-κB were attenuated, cell apoptosis, proliferation, and migration were decreased. After pretreated with compound C, the reverse effects occurred. p-AMPKα and SIRT1 expressions were decreased, ace-p53 and ace-NF-κB were rasied, and cell apoptosis, proliferation, and migration were enhanced after caerulein induced in each group. Conclusion: When AP happened, expressions of p-AMPKα and SIRT1 were reduced, resulting in up-regulation of acetylation levels of p53 and NF-κB, acceleration of cell apoptosis, proliferation and migration. It hinted that AMPK-SIRT1 pathway could modulate the apoptosis, proliferation, migration and inflammation reaction of AR42J cells by regulating p53 and NF-κB.

Synergistic antitumor effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines via modulation of the AMPK/VEGF/ERK/NFKB/caspase-3 signaling axis

“…The present study also revealed a considerable decrease in NF-κB levels as a nal RAS/ERK signaling substrate. This inhibition is due to the inhibitory effects of AMPK on NF-κB signaling, which are mediated by multiple downstream targets such as SIRT1, PGC-1alpha and p53 [22].…”