OBJECTIVE To explore the regulatory effect of Luteolin on the inflammation-cancer transformation in chronic gastritis and its underlying mechanism involving the JAK2/STAT3 pathway.
METHODS Network pharmacology was used to identify common 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 viability was measured by CCK-8, and oncogene expression was analyzed by qPCR to determine optimal MNNG concentration and induction 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.
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