Dataset Information

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer.

ABSTRACT: Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, ?-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter <2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.

SUBMITTER: Huang JR

PROVIDER: S-EPMC7748110 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer.

Huang Jia-Rong JR Wang Sheng-Te ST Wei Meng-Ning MN Liu Kun K Fu Jing-Wen JW Xing Zi-Hao ZH Shi Zhi Z

Frontiers in pharmacology 20201112

Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) o ...[more]

PMID: 33343354

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Project description:BackgroundUlcerative colitis (UC) is a chronic inflammatory disease of the intestinal mucosa, the incidence of which has increased worldwide. There is still a lack of clear understanding of the pathogenesis of ulcerative colitis that ultimately leads to colitis-associated colorectal cancer.MethodWe download UC transcriptome data from the GEO database and pass the limma package in order to identify differentially expressed genes. Gene Set Enrichment Analysis (GSEA) was used to identify potential biological pathways. We identified immune cells associated with UC by CIBERSORT and Weighted co-expression network analysis (WGCNA). We used validation cohorts and mouse models to verify the expression of the hub genes and the role of neutrophils.ResultWe identified 65 differentially expressed genes in UC samples and healthy controls. GSEA, KEGG, and GO analyses displayed that DEGs were enriched in immune-related pathways. CIBERSORT analysis revealed increased infiltration of neutrophils in UC tissues. The red module, obtained by WGCNA analysis, was considered to be the most relevant module for neutrophils.Based on neutrophil-associated differentially expressed genes, UC patients were classified into two subtypes of neutrophil infiltration. We discovered that the highly neutrophil-infiltrated subtype B of UC patients had a higher risk of developing CAC. Five genes were identified as biomarkers by searching for DEGs between distinct subtypes. Finally, using the mouse model, we determined the expression of these five genes in the control, DSS, and AOM/DSS groups. The degree of neutrophil infiltration in mice and the percentage of MPO and pSTAT3 expression in neutrophils were analyzed by flow cytometry. In the AOM/DSS model, MPO and pSTAT3 expressions were significantly increased.ConclusionsThese findings suggested neutrophils might promote the conversion of UC into CAC. These findings improve our understanding of the pathogenesis of CAC and provide new and more effective insights into the prevention and treatment of CAC.

Dataset Information

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer.

Publications

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer.

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