Effect of Aspirin on G0/G1 Cell Cycle Arrest and microRNA Signatures in Pancreatic Adenocarcinoma Cells.

Abstract

Anti-inflammatory drugs, such as aspirin, have attracted attention as anticancer agents that can be applied to standard chemotherapy for pancreatic cancer. This study aimed to examine the antitumour effects and possible fundamental mechanisms of aspirin in pancreatic cancer cells. We appraised the antitumour effects of aspirin on cell proliferation and tumour growth, cell cycle distribution, apoptosis, signalling pathways, angiogenesis-related proteins, and phosphorylated receptor tyrosine kinases (p-RTKs) and identify miRNAs associated with its antitumour effects. Aspirin inhibited cell proliferation in pancreatic cancer cell lines and induced G0/G1 cell cycle arrest by decreasing the expression of cyclin D1. Aspirin inactivated glycogen synthase kinase (GSK)-3β but had no effect on the p38 mitogen-activated protein kinase (MAPK) pathway, p-RTKs, or angiogenesis-related molecules. Aspirin treatment statistically increased the expression of 274 miRNAs in PANC-1 cells and 30 miRNAs in PK-8 cells and suppressed the expression of 294 miRNAs in PANC-1 cells and 13 miRNAs in PK-8 cells. Aspirin inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest. Aspirin also inactivated GSK-3β but not the p38 MAPK pathway. Thus, aspirin may be used in combination with chemotherapeutic agents for pancreatic cancer.