Study Of Resveratrol Through Multi-Target Of SIRT1-NF-κB Pathway Anti Colon Cancer Invasion And Metastasis

Objective:Our objective is to expound the target protein and the mechanism of Resveratrol on epithelial mesenchymal transition(EMT)related signaling pathways and regulatory proteins based on SIRT1-NF-κB,and to lay the theoretical foundation for the further promotion of the clinical application.Methods: We use EMT model of colon cancer cell SW620、HCT8 induced by EGF in our study,and construct SIRT1.We observe the different effect of Resveratrol on SW680、HCT8 cells by the scratch test,Transwell migration assay and invasion assay,laser confocal microscope,Western Blot.Results:(1)The SW620、HCT8 cell line stably transfected with SIRT1-RNAi Lentivirus in human colon cancer was successfully established,and SIRT1 gene and protein were all lowly expressed.(2)The scratch results: SW620,HCT8 12 h and 24 h cell migration distance,resveratrol group < blank group <model group.the model group compared with the control group,with enhanced migration trend,but no statistically significant difference;resveratrol group than the control group the distance was shortened,the difference was significant(P<0.05);resveratrol group compared with the model group,the distance is shortened obviously,there were significant differences(P<0.05).However,there was no statistical difference in the SIRT1 silence in each group.(3)The results of cell Transwell experiment: the number of SW620 and HCT8 cells migrated over the membrane,and the resveratrol group < blank group <model group.Among them,the model group than the control group.Cell number increased,but no significant difference statistically;resveratrol group compared with control group,cell membrane was significantly reduced,there were significant differences(P <0.05);resveratrol group than in model group compared to the membrane of cells decreased significantly statistically significant difference(P <0.05).However,there was no statistical difference in the SIRT1 silence in each group.(4)The results of cell Transwell experiment :The number of SW620 and HCT8 cells migrated over the membrane,and the resveratrol group < blank group < model group.Among them,the model group than the control group.Cell number increased,but no significant difference statistically;resveratrol group compared with control group,cell membrane was significantly reduced,there were significant differences(P<0.05);resveratrol group than in model group compared to the membrane of cells decreased significantly statistically significant difference(P <0.05).However,there was no statistical difference in the SIRT1 silence in each group.(5)The results of Western Blot:The expression of Fibronectin and N-Cadherin in the SW620 and HCT8 cell model group was increased compared with the blank group,and the expression of E-Cadherin decreased.The difference was statistically significant(p<0.05),indicating that EGF induced SW620 epithelial cell transformation in SW620 group.Compared with EGF model group,resveratrol group significantly enhanced E-Cadherin and reduced Fibronectin and N-Cadherin expression,and the difference was statistically significant(p<0.05),but the difference is obviously reduced.Conclusions:(1)resveratrol can inhibit the migration and invasion of SW620 and HCT8 cells in colon cancer.(2)Resveratrol can reverse the EMT of SW620 and HCT8 by EGF.(3)After SIRT1 silence,the ability of resveratrol to reverse EMT is weakened.It is clear that resveratrol can reverse EMT action of SW480 and HCT8 cells through SIRT1-NF-kappa B pathway.(4)After SIRT1 silence in SIRT1-NF-kappa B pathway,resveratrol inhibited the migration and invasion ability of SW620 and HCT8 cells,which was weaker than that before silencing.It was clear that resveratrol inhibited the migration and invasion of SW620 and HCT8 cells through SIRT1-NF-kappa B pathway.