| Colorectal cancer(CRC)is the third most common malignancy in the world.Its mortality rate is in the fourth place.CRC patients increase year by year.In China,it has been the third largest risk of cancer.CRC formation is a multi-factor,multi-step process.Inflammatory bowel disease(IBD)and family genetic history are the largest risk factors of CRC.IBD patients are more likely to suffer from colorectal cancer compared with normal people.Inflammation can promote the development of tumors.Different immune cells,cytokines,and other immune mediators play a very important role in the initiation,formation,development and metastasis of tumors.Surgery is still the main treatment for colorectal cancer currently assisted with chemotherapy and radiotherapy,but the effect is limitation.Metastasis is an important cause of the death in patients with colorectal cancer.More than half of patients with colorectal cancer before surgery have been the recurrence because of metastasis.Therefore,to find an effective oral medicine to prevent and treat colorectal cancer is of great significance.Tea polyphenols are a class of polyphenols in tea.Chinese people have been thousands of years of using tea history.Studies have shown that tea polyphenols have an inhibitory effect on proliferation,metastasis of a variety of cancer cell.In this study,BALB/c mice were randomly divided into normal group,hyperlipidemia group,low-fat model group,high-fat model group and tea polyphenol.Colorectal cancer models were established by intraperitoneal injection of oxidized azobenzene(AOM)and drinking 2%sodium dextran sulfate(DSS)with three cycles.For more close to the formation process of human body colitis associated colorectal cancer(colitis associated colorectal cancer,CAC),mice were given a high-fat diet for long-term.After the establishment of the model,the effects of CRC and tea polyphenols on dietary effects and dietary factors were investigated at the molecular level and the individual level.The specific work was as follows:1.The establishment mouse model of colitis-associated colorectal cancer.The acute inflammation model of mice was established by single treatment of AOM/DSS.The whole process of spontaneous IBD-related CRC was simulated by repeated treatment of long-term high-fat diet(60 kcal%).The results showed that diarrhea,hematochezia and weight loss were significantly higher in the disease activity index(DAI)of mice fed with high fat diet than that in the mice fed with low-fat diet after single treatment of AOM/DSS.High fat diet increased the incidence of intestinal inflammation in some degree.At the end of the experimental cycle,AOM/DSS-treated mice were found to have different sizes of colorectal tumors,indicating that the CAC model was successfully established.2.Correlation study with high fat diet,inflammation and colorectal cancer.The inflammatory response and tumor formation were compared by qRT-PCR and histopathological observation.The results showed that inflammatory cell infiltration could be seen in colorectal tissue sections of high-fat group,low-fat model group,high-fat model group and tea polyphenol group.Glandular body was also seen in high fat model group,so called atypical hyperplasia.The degree of inflammation in each group is proportional to the number of tumors,indicating that the inflammatory response can promote the formation of the tumor.3.Wnt signal pathway activation.In this study,the expressions of p-GSK-3? and?-catenin,two key components of Wnt signaling,were detected by qRT-PCR in the downstream target gene C-myc and Cox-2.Western Blot of Wnt signaling pathway was used to detect Wnt signaling pathway activation.The results showed the stronger inflammatory response,the more intracellular accumulation of ?-catenin,and the expression of downstream target genes was also up-regulated under this condition,indicating that the inflammatory response promotes the activation of the Wnt signaling pathway.4.Investigate the anti-inflammation and anti-cancer effects of tea polyphenols.During the establishment of the CAC,the tea polyphenols treatment group was treated with 0.1%tea polyphenols aqueous solution.Compared with the low-fat model group and the high-fat model group,the relative expression of pro-inflammatory factors was down-regulated in the tea polyphenols group.The relative expression of the anti-inflammatory factors was up-regulated.The accumulation of ?-catenin in tea polyphenols group was significantly lower than that in high-fat model group and low fat-model group,and the relative expression of downstream target gene of Wnt signal was also down-regulated.The above results show that tea polyphenols inhibit the occurrence of inflammatory response to a certain extent,and then inhibit the activation of Wnt signaling pathway. |
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