Abstract
Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus, has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1β, and IL-18 in the colon of CAC mice. Moreover, in vitro, IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.
Highlights
Colorectal cancer is one of the leading causes of cancer death worldwide (Saif et al, 2006; Chen et al, 2016)
Immunohistochemical analysis indicated colons of Inonotus obliquus polysaccharide (IOP) group contained significantly more cells staining positive for NLRP3 inflammasome, IL-1β and IL-18 (Figures 3H,I). These results demonstrated that IOP can promote the activation of NLRP3 inflammasomes induced by AOM/DSS, providing a potential mechanism for studying the benefits of IOP in the development of CAC
The mechanisms by which chronic inflammation leads to carcinogenesis are complex
Summary
Colorectal cancer is one of the leading causes of cancer death worldwide (Saif et al, 2006; Chen et al, 2016). Colitis-associated cancer (CAC) frequently develops in patients with long-term intestinal inflammation, for example, those with inflammatory bowel disease (IBD), and tumors may form at other sites in the body. CAC is a leading complication of IBD, and its incidence and mortality rates have increased steadily (Leong et al, 2004). The link between chronic inflammation and cancer, including various theories about the progression of IBD to CAC, is not well understood. We focused on the potential mechanism of NLRP3 inflammasomes in the process of connecting IBD and CAC. There are many inflammasomes, the most widely studied is the NLRP3 inflammasome
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