Mechanism of antitumor efficacy of Wogonin in suppressing colorectal cancer by regulating gut microbiota
Objective:To investigate the mechanism of Wogonin in regulating gut microbiota and suppressing colorectal cancer(CRC)tumor formation.Methods:APCmin+gene-deficient mouse model and AOM/DSS inflammatory cancer transformation mouse model were established,and 0.2％DCA was used for modeling.The mice were randomly divided into normal,model,and high/low-dose Wogonin groups and given the corresponding drugs.Mouse status was observed every other day.After euthanizing the mice,colorectal tissue was obtained to observe the histopathological changes with HE staining,detect F4/80 and Mannose expression in tumor tissue with immunofluorescence staining,and observe the effect of Wogonin on tumor cell apoptosis with TUNEL staining.Changes in gut microbiota of mice in each group were detected by 16S rRNA sequencing technology,and bioinformatics analysis was performed.Results:Compared to the control group,DCA intervention significantly promoted CRC development.However,Wogonin significantly reduced the volume of colorectal cancer tumors(P＜0.01).HE and TUNEL staining results showed that DCA intervention reduced tumor cell apoptosis,while Wogonin induced tumor cell apoptosis.Immunofluorescence staining results showed that DCA intervention increased the expression of F4/80 and Mannose in mouse tumor tissue,while the expression of F4/80 and Mannose in the Wogonin treatment group was significantly reduced.LEfSe analysis suggested that after DCA modeling,the relative abundance of Ruminococcaceae_UCG-014 decreased,and Muribaculum significantly increased.Compared to the model group,the high-dose Wogonin intervention significantly downregulated Escherichia-Shigella and Parabacteroides and upregulated Ileibacterium and Ruminococcaceae_UCG-014.KEGG enrichment results indicated that the regulation of CRC-related gut microbiota was closely related to carbohydrate metabolism,cancer pathways,and amino acid metabolism.Conclusion:Wogonin can inhibit the occurrence of colorectal cancer mediated by DCA by regulating intestinal flora.
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