基于网络药理学探讨木犀草素干预慢性胃炎"炎-癌转化"的作用机制OA

OBJECTIVE To explore the regulatory effect of Luteolin on the inflammation-cancer transformation in chronic gastri-tis and its underlying mechanism involving the JAK2/STAT3 pathway.METHODS Network pharmacology was used to identify com-mon key targets of Luteolin in chronic atrophic gastritis(CAG)and gastric cancer(GC).A PPI network was constructed to predict core targets and their relationship with the JAK2/STAT3 pathway.KEGG and GO analyses were performed to explore related pathways and biological functions,and molecular docking was used to verify binding affinity.Human gastric mucosal epithelial cells(GES-1)were cultured,and N-methyl-N´-nitro-N-nitrosoguanidine(MNNG)was used to induce inflammation-carcinoma transformation.Cell vi-ability was measured by CCK-8,and oncogene expression was analyzed by qPCR to determine optimal MNNG concentration and induc-tion time.The effects of different Luteolin concentrations on cell viability were evaluated by CCK-8,and qPCR was used to detect JAK2/STAT3 pathway-related gene expression.RESULTS Luteolin,CAG,and GC shared 31 common targets,and Luteolin docked well with JAK2,STAT3,MET,and MMP2 molecules.The optimal conditions for MNNG-induced inflammation-cancer transformation in GES-1 cells were:MNNG intervention at 40 μmol·L ⁻ ¹ for 24 h,followed by cell culture for 6 days.Administration of Luteolin at concentrations of 4,8,12 μmol·L ⁻ ¹ improved cell growth and inhibited the expression of JAK2,STAT3,MET,and MMP2.CONCLUSION Certain concentrations of Luteolin regulate the inflammation-cancer transformation process in chronic gastritis,and its effect is related to the regulation of the JAK2/STAT3 pathway.