| Colorectal cancer(CRC)is one of the most common malignant tumor in the world,especially in Western countries.Its mortality rate ranks in the top three in the world.CRC is divided into sporadic colon cancer and colitis-related cancers.The predisposing factors include environment,diet,genetic susceptibility,intestinal mucosal damage,and intestinal dysbacteriosis.In recent years,as colorectal cancer has become more and more concerned,Traditional Chinese medicine has also played an increasingly important role in the prevention and treatment of colorectal cancer.Sini Tang is a classic and famous prescription in Zhang Zhongjing's Treatise on Febrile Diseases.It is mainly composed of aconite,dried ginger and licorice.Studies have shown that Sini Decoction has many pharmacological effects,contains anti-tumor,anti-shock,anti-atherosclerosis,protection of intestinal mucosa,immune regulation and other.In this study,we used AOM-DSS to induce the establishment of a mouse CRC model to investigate the effect of Sini Tang on CRC in mice and its effect on the gut microbiota in mice to further explore its possible mechanism of action.During the modeling process,the mice were monitored daily for changes in body weight,and after the completion of the modeling,the weight gain percentage of the mice before and after the experiment was counted;the colon was taken,photographed,HE staining was performed for histopathological examination,and the weight of the colon unit was counted to judge the Pharmacodynamic effects of Sini Tang on CRC mice.The results showed that Sini Tang can increase the body weight of mice with CRC to some extent,improve the quality of life of mice,and reduce the unit weight of the colon.It can be seen from the phenotype of colon that the number of colon tumors treated with Sini decoction is significantly reduced and the volume is reduced.From the pathological point of view,the malignant degree of colon cancer in the treatment group was improved,indicating that Sini Tang can significantly improve mouse CRC induced by AOM and DSS.Therefore,we further explored the mechanism of action of Sini Tang against colon cancer from the aspects of cytokines,immunity,intestinal barrier and intestinal flora.The expression of cytokines was detected by ELISA.The expressions of COX-2 and MUC2 were detected by RT-PCR.The expressions of CD4,CD8 and Occludin were detected by immunohistochemistry.The results showed that Sini Tang can inhibit the secretion of pro-inflammatory cytokines IL-6,IL-17,TNF-? and IFN-? in colon cancer tissue of mice,down-regulate the expression of COX-2 and MUC2,and increase the number of CD4+ and CD8+ T lymphocytes.The expression of the tight junction protein Occludin in colonic epithelial cells and the mucosal layer was increased.In addition,16SV4 region amplicon sequencing was used to detect changes of gut microbiota in mouse feces samples,and RT-PCR was used to detect several intestinal bacteria that were important for colon cancer.It was found that Sini Decoction can change the composition of the gut microbiota in mice with CRC,reduce the number of pathogenic bacteria Bacteroides fragilis and Sulphate-reducing bacteria(SRB),and increase the relative contents of the beneficial bacteria Lactobacillus,Bacillus coagulan,Akkermansia muciniphila,and Bifidobacterium.Taken together,Sini Tang may exert its effects by enhancing intestinal immunity,inhibiting the secretion of pro-inflammatory cytokines,down-regulating the colon cancer marker genes,protecting the colon mucosal barrier,and changing the composition of the intestinal flora,reducing pathogenic bacteria,and increasing beneficial bacteria to alleviate CRC in mice. |
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