Study On Effect And Mechanism Of SBJDF In Inhibiting The Canceration Of Colorectal Adenoma Based On The Inflammation-induced Carcinogenesis

Objective:To explore the effect and mechanism of SBJDF in inhibiting the canceration of colorectal adenoma based on the inflammation-induced carcinogenesisMethods:1.The carcinogenic effects of azomethane oxide(AOM),combined with the intestinal mucosal damage and pro-inflammatory effects of Dextran Sodium Sulfate(DSS).Which used to induce colorectal adenomas and further form colorectal cancer in C57BL/6 mice.Mice were randomly divided into 5 groups:blank group,model group,low-dose group of SBJDF,high-dose group of SBJDF,and positive control group.The mice were sacrificed at the end of experiment.The histopathology of the mice was observed by HE staining.The expression of PCNA and Ki-67 was detected by immunohistochemistry.The protein expression of PTEN,AKT,P-AKT,PCNA,P65 and P-P65 was detected by western blotting.2.DSS solution was used to induce human normal colorectal mucosal epithelial cells(FHC)injury,MTT experiment was used to detect the effect of DSS on FHC cell viability;EdU was used to detect the effect of SBJDF on the proliferation of FHC cells after injury;Flow cytometry The effect of SBJDF on the distribution of FHC cell cycle after injury was detected;Western blotting was used to detect the effect of SBJDF on the expression of Cyclin A2,CDK1,P65 and P-P65 protein in FHC cells after injury.3.The effect of SBJDF on the proliferation of HCT116 cells was detected by MTT method,cell morphology was observed by inverted microscope;Cell apoptosis was detected by flow cytometry;The protein expression of cell anti-apoptosis related proteins BCL-2,BCL-XL,PTEN,AKT,P-AKT,P65 and P-P65 were detected by Western blotting.Results:1.SBJDF can improve the general condition of adenoma carcinogenesis model mice and reduce mortality;effectively inhibit the proliferation and number of colorectal mucosal adenomas in model mice,and reduce the pathological degree of adenomas in model mice;reduce the intestinal tract of model mice Ki-67 and PCNA positive cells are expressed in tissues.SBJDF increases the expression of PTEN protein in the intestinal tissues of model mice,and reduces the ratio of P-AKT/AKT and P-P65/P65.2.SBJDF reduces the toxic effects of DSS and restores cell viability;reverses the cell cycle G0/G1 block caused by DSS;DSS reduces the number of EdU-positive cells in FHC,and SBJDF increases the number of EdU-positive FHC cells after DSS treatment;SBJDF DSS model group down-regulates the expression of Cyclin A2 and CDK1 protein in FHC cells,and the ratio of P-P65/P65 increases.SBJDF up-regulates the expression of Cyclin A2 and CDK1 protein in FHC cells after DSS treatment.reduces the ratio of P-P65/P65.3.SBJDF inhibits the proliferation of HCT116 cells,changes cell morphology,and induces apoptosis after intervention;reduces the expression of BCL-2 and BCL-XL in HCT116 cells;increases the expression of PTEN in HCT116 cells,reduces the ratio of P-AKT/AKT and the ratio of P-P65/P65.Conclussion:1.SBJDF can effectively inhibit the number and size of colorectal adenomas in model mice,and reduce the pathological degree of adenomas;its mechanism of action may be to activate PTEN expression,inhibit PI3K/AKT signaling pathway,and regulate NF-κB signaling pathway.2.SBJDF can reverse the cell cycle block caused by DSS,regulate the NF-κB signaling pathway,and protect the mucosal epithelial cells of ulcerative colitis.3.SBJDF inhibits the proliferation of HCT116 cells and induces cell apoptosis,which may be related to its regulation of PTEN/PI3K/AKT signaling pathway and NF-κB signaling pathway.