结肠炎
TLR4型
医学
癌变
炎症
肿瘤坏死因子α
癌症研究
结直肠癌
脂多糖
癌症
促炎细胞因子
免疫学
内科学
作者
Li Liu,Yuhua Li,Youguo Niu,Yang Sun,Zengjun Guo,Qian Li,Chen Li,Juan Feng,Shousong Cao,Qibing Mei
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2010-04-16
卷期号:31 (10): 1822-1832
被引量:97
标识
DOI:10.1093/carcin/bgq070
摘要
Evidence strongly supported a link between inflammation and cancer. Patients with colitis have high risk for development of colon cancer. Nuclear factor-kappa B (NF-κB), partially induced by lipopolysaccharide (LPS) binding to Toll-like receptor (TLR) 4, is a vital molecule in supervising the transformation of colitis to colon cancer. It could be a good strategy to prevent colitis carcinogenesis for targeting LPS/TLR4/NF-κB pathway. In the present study, we obtained an oligogalactan composed of five galacturonic acids from apple pectin and evaluated its protective efficacy on intestinal toxicities and carcinogenesis in a mouse model of colitis-associated colon cancer induced by 1,2-dimethylhydrazine and dextran sodium sulfate (DSS). The apple oligogalactan (AOG) was highly effective against intestinal toxicities and carcinogenesis and decreased the elevated levels of TLR4 and tumor necrosis factor-α (TNF-α) induced by inflammation in vivo in this model system. In vitro studies, AOG alone only slightly increased the levels of protein expression and messenger RNA of TLR4, phosphorylation of IκBα and production of TNF-α in HT-29 cells. However, AOG significantly decreased the elevation of all the biomarkers induced by LPS when it was combined with LPS. The effect of AOG may be related to membrane internalization and redistribution of TLR4 from cell membrane to cytoplasm. AOG is active against inflammation and carcinogenesis through targeting LPS/TLR4/NF-κB pathway. Both AOG and LPS are agonists of TLR4 for sharing the same ligand but AOG has a much lower intrinsic activity than that of LPS. AOG may be useful for treatment of colitis and prevention of carcinogenesis in the clinics.
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