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

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)-alpha, interleukin(IL)-1(3, 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 COStreated CAC mice. COS administration significantly down-regulated expression of micro(mi)RNA-155, toll-like receptor(TLR)4, nuclear factor-kappaB(NF-kappa B), 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.