Anti-proliferation effect of chitooligosaccharide on colitis-associated cancer in mice: Possible involvement of miRNA-155/TLR4/Reg3g pathway

Abstract

Chronic colonic inflammation might result in increased cell proliferation that poses risk of colitis-associated cancer(CAC), an aggressive subtype of colorectal cancer. This study aimed to investigate dietary intervention effect and mechanism of chitooligosaccharide(COS) on azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced CAC development in mice. COS at dose of 500 mg/kg markedly suppressed colonic levels of tumor necrosis factor(TNF)-α, interleukin(IL)-1β, and IL-6 in CAC mice. Compared to CAC model controls, the number of colonic epithelial cells expressing Ki-67 and the colonic expression levels of cyclin D1 were decreased in COS-treated CAC mice. COS administration significantly down-regulated expression of micro(mi)RNA-155, toll-like receptor(TLR)4, nuclear factor-kappaB(NF-κB), phosphorylated signal transducer and activator of transcription protein 3(pSTAT3), and regenerating islet derived 3 gamma(Reg3g), whereas up-regulated the suppressors of cytokine signaling 1 (SOCS1) expression in CAC colons. Overall, COS exerted protective activity against AOM/DSS-induced colitis-associated carcinogenesis, mechanism of which was associated with its anti-proliferation effect possible via regulating miRNA-155/TLR4/Reg3g pathway.

Keywords

• Chitooligosaccharide
• Colitis-associated cancer
• MicroRNA-155
• TLR4
• Regenerating islet derived 3 gamma