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.
Highlights
Colorectal cancer (CRC) is one of the most common gastrointestinal malignant cancers and is a leading cause of cancer-related mortality across the globe [1]
The Western diet (WD) + AOM/dextran sulfate sodium (DSS) group showed multiple nodular masses in their colon tissues compared to the AOM/DSS group, implying that WD consumption elevated susceptibility to tumorigenesis (Figure 1E)
There were no significant differences between the AOM/DSS and WD + AOM/DSS groups in terms of fat pad weight (Figure 1G,H)
Summary
Colorectal cancer (CRC) is one of the most common gastrointestinal malignant cancers and is a leading cause of cancer-related mortality across the globe [1]. This malignancy is a serious complication of inflammatory bowel disease (IBD), and the risk of CRC is related to the severity, extent, and duration of IBD [2]. It has been reported that 5-acetylsalicylic acid (5-ASA), a medication used to treat IBD, represses the progression of ulcerative colitis (UC) to CRC, suggesting a promising therapeutic approach to anti-inflammatory drugs for CRC treatment [4]. Chemotherapy drugs, including camptothecin (CPT), are most often used to treat CRC. It is essential to develop new agents with low risk and toxicity
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