Mechanism Of PPAR? Agonist Enhances Colitis-associated Colorectal Cancer

Peroxisome proliferator-activated receptor-?(PPAR?)acts as a nuclear receptor and plays an important role in inflammation and tumorigenesis.However,it is unclear the effect of PPAR? agonist GW501516 on colitis-associated colorectal cancer.This study found that GW501516 enhanced DSS-induced colitis.In addition,GW501516 enhanced AOM/DSS-induced colitis-associated colorectal cancer,which was associated with an increase in the expression of Glut1 and SLC1A5.The significant findings are as follows:1.In the DSS-induced colitis model,PPAR? agonist GW501516 significantly enhanced DSS-induced colitis.In addition,HE staining shows that GW501516 significantly disrupted intestinal mucosal integrity.2.The analysis of immunohistochemistry and Western Blot shows that GW501516 significantly increased PCNA and Ki67 expressions of intestinal epithelial cells.3.q-PCR analysis by extraction of mice colonic epithelial cells revealed that GW501516 significantly enhanced the expressions of inflammatory factors(IL-6,IL-8,COX-2,MCP-1).4.In AOM/DSS-induced colitis-associated colorectal cancer model,GW501516 significantly enhanced AOM/DSS-induced colorectal cancer progression.5.Dual-luciferase and Western Blot analysis show that GW501516 enhanced the transcriptional activity of PPAR? and enhanced the expressions of Glut1 and SLC1A5 in colorectal cancer cells and tumor tissues.These findings suggest that GW501516 enhanced AOM/DSS-inudced colitis-associated colorectal cancer involved in increased Glut1 and SLC1A5 expressiosns,which revealed a novel mechanism of PPAR? agonist GW501516-mediated colitis-associated colorectal cancer.