Anti‐obesity drug orlistat alleviates western‐diet‐driven colitis‐associated colon cancer via inhibition of stat3 and nf‐κb‐mediated signaling

Abstract

Many researchers have argued that Western diet (WD)‐induced obesity accelerates inflammation and that inflammation is a link between obesity and colorectal cancer (CRC). This study investigated the effect of WDs on the development and progression of colitis‐associated colon cancer (CAC) and the efficacy of the anti‐obesity agent orlistat on WD‐driven CAC in mice. The results revealed that the WD exacerbated CAC in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced mice, which showed increased mortality, tumor formation, and aggravation of tumor progression. Furthermore, WD feeding also upregulated inflammation, hyperplasia, and tumorigenicity levels through the activation of STAT3 and NF‐κB signaling in an AOM/DSS‐induced mouse model. In contrast, treatment with orlistat increased the survival rate and alleviated the symptoms of CAC, including a recovery in colon length and tumor production decreases in WD‐driven AOM/DSS‐induced mice. Additionally, orlistat inhibited the extent of inflammation, hyperplasia, and tumor progression via the inhibition of STAT3 and NF‐κB activation. Treatment with orlistat also suppressed the β‐catenin, slug, XIAP, Cdk4, cyclin D, and Bcl‐2 protein levels in WD‐driven AOM/DSS‐induced mice. The results of this study indicate that orlistat alleviates colon cancer promotion in WD‐driven CAC mice by suppressing inflammation, especially by inhibiting STAT3 and NF‐κB activation.