基于肠道菌群介导的炎性反应研究黄芪多糖对结肠炎相关癌症的作用

目的:探讨黄芪多糖(APS)对结肠炎相关癌(CAC)小鼠和结肠癌细胞中肠道细菌诱导的Toll样受体-4/核因子-κB(TLR4/NF-κB)信号通路的影响.方法:将40只C57BL/6J雄性小鼠随机分为对照组(n=10),模型组(n=15)和APS组(n=15).模型组和APS组由氧化偶氮甲烷和葡聚糖硫酸钠制成CAC模...

Study on the Mechanism of Astragalus Polysaccharide on Colitis-Related Cancer Based on the Inflammatory Response Mediated By Intestinal Flora

Objective:To explore the effects of Astragalus polysaccharide(APS)on intestinal bacteria induced Toll-like reeeptor-4/nuclear factor-κB(TLR4/NF-κB)signaling pathway in colitis-associated cancer(CAC)mice and colon cancer cells.Methods:A total of 40 C57BL/6J male mice were randomLy divided into a control group(10 mice),a model group(15 mice),and an APS group(15 mice).The model group and APS group were made CAC model by azoxymethane and sodium dextran sulfate.The control group and model group were given 0.9%sodium chloride injection,and the APS group was given 100 mg/kg APS by gavage for 14 days.In this study,the Histopathological Examination method was used to detect the pathological conditions of colorectal in mice.Characteristics of intestinal flora were analyzed by 16S rDNA sequencing.Lipopolysaccharide concentrations were determined by enzyme 1inked immunosorbent assay.Expressions of TLR4 and NF-κB p65 proteins in colon tissue were detected by immunohistochemistry.In the in vitro study,we further validated the effects of APS on proliferation and migration of human colon cancer cells.The MTT assay and Scratch test were used to evaluate cell viability assays.The nuclear translocation of NF-κB p65 was detected by immunofluorescence.Western blot was used to detect the expression of E-cadherin and N-cadherin proteins.Results:Sequencing results showed that Gram-negative bacteria(Bacteroides)were commonly detected in the model group,and intestinal flora in APS group were mostly Gram-positive bacteria(Lactococcus and Bifidobacterium).Expression levels of LPS,TLR4,and NF-κB p65 proteins in APS group were significantly lower than those in the model group.APS can inhibit the proliferation and migration of LoVo cells and HCT116 cells;APS(40μg/mL)can inhibit the nuclear translocation of NF-κB,reduce the expression of N-cadherin protein,and increase the expression of E-cadherin protein.Conclusion:APS can prevent CAC by inhibiting Gram-negative pathogens,reducing the release of LPS and inhibiting TLR4/NF-κB signaling pathway.And APS can effectively inhibit the EMT process of human colon cancer cells and effectively control tumor proliferation and migration.