Based On STAT-3/NF-κB/ICAM-1 Pathway To Explore The Mechanism Of Paeonol Inalleviating Colitis-Related Colorectal Cancer

Objective :To study the colitis-cancer transformation model,and the mechanism of paeonol in the treatment of colitis-cancer transformation,and to clarify the effect of STAT-3/NF-κB/ICAM-1 signaling pathway alleviating colitis-cancer transformation.Methods:1.With the AOM/DSS to construct a mice mouse model of colitis-cancer and observe the general signs of mice,ELISA kit was used to measure serum TNF-α、IL-6、IL-1β and IL-10 levels in mice,HE pathological changes of colonic tissue in mice were observed under microscope;The expression levels of STAT-3,NF-κBp65 and ICAM-1protein in colon tissues of mice was detected by Western blot and IHC methods.2.After the co-culture of Caco-2cells and paeonol induced by LPS,TNF-α、IL-6、IL-1β and IL-10 levels in Caco-2 cells detected by the kit.The protein expression level of STAT-3,NF-κBp65 and ICAM-1 were detected by Western blot methods.Flow cytometry was used to analysis cell apoptosis after fluorescence double staining.Results:1.Under the induction of AOM/DSS,the serum contents of TNF-α,IL-6 and IL-1β increased significantly while IL-10 serum levels decreased significantly.Both positive cell and protein expression levels of STAT-3,NF-κBp65 and ICAM-1 were significantly increased.Taking mesalazine as a positive reference,after intervention of paeonol,under the light microscope,the inflammatory cell infiltration of mice colon were obviously alleviated.The weight of mice in each group increased obviously,especially in the middle-dose group;after the intervention of paeonol,the disease activity index of mice in each group reduced significantly,among which in the middle-dose group.After the intervention of paeonol,the number of tumors on the colon in each group was less than that in the model group,and the spleen index was decreased particularly(P<0.05);After the intervention of paeonol,TNF-α,IL-6 and IL-1β serum content was significantly reduced(P<0.05),and serum content of IL-10 increased significantly(P<0.05).The protein expression levels of STAT-3,NF-κBp65 and ICAM-1 in colon of mice were significantly lower than those in model group after paeonol intervention(P<0.05).2.After Caco-2 cells being induced by LPS,TNF-α、IL-6 and IL-1β serum levels increased obviously while IL-10 serum levels decreased particularly.After the intervention of paeonol,TNF-α,IL-6 And IL-1β serum content was significantly reduced,and IL-10 serum content was significantly increased.The expression levels of STAT-3,NF-κBp65 and ICAM-1 proteins increased significantly after LPS induction.Taking the STAT-3 inhibitor AG490 as a reference,after paeonol treatment,the protein levels of STAT-3,NF-κBp65 and ICAM-1 increased particularly.The result of flow cytometry showed that the ratio of Caco-2 cells apoptosis in the model group after LPS induction was significantly higher than the blank group,and the apoptosis was inhibited after the intervention of paeonol.Conclusion :Paeonol can effectively relieve the inflammatory reaction of ulcerative colitis,the mechanism of which is associated with its interference with STAT-3/NF-κB/ICAM-1 signaling pathway.