Efficacy and mechanism of dihydrotanshinone Ⅰ in the treatment of precancerous lesions of gastric cancer

MENG Xiangmei; CHU Fuhao; ZHENG Haocheng; CHEN Jiena; LIN Jie; LI Tao; DING Xia

doi:10.13506/j.cnki.jpr.2025.04.002

Abstract：Objective To explore the efficacy and mechanism of action of dihydroartemisinin Ⅰ on the precancerous lesions of gastric cancer.Methods Normal gastric epithelial cells GES-1 were induced with 20 μmol·L-1 MNNG for 24 hours to construct precancerous cells,followed by intervention with different doses of dihydroartemisinin Ⅰ.Cell proliferation capacity was evaluated using CCK-8 and colony formation assays,cell migration ability was assessed using the scratch as-say,and apoptosis was detected using flow cytometry.Additionally,changes in the expression of N-cadherin,E-cadherin,Bcl2,and Bax were examined using Western blotting.Transcriptome sequencing,molecular docking,molecular dynamics,and isothermal titration calorimetry were employed to explore the key pathways and protein changes in MC cells after dihydroar-temisinin Ⅰ intervention.Results The precancerous cell model MC was successfully established.Dihydroartemisinin Ⅰ sig-nificantly inhibited the proliferation and migration abilities of MC cells and promoted cell apoptosis.Transcriptome sequen-cing results revealed that differentially expressed genes after dihydroartemisinin Ⅰ intervention primarily focused on the p53 signaling pathway,cell apoptosis,inositol phosphate metabolism pathway,and EGFR signaling pathway.Furthermore,di-hydroartemisinin Ⅰ intervention promoted the expression of p53 in MC cells,reduced the expression of MDM2,thereby in-terfering with the p53/MDM2 feedback loop in MC.Additionally,dihydroartemisinin Ⅰ exhibited high affinity with the MDM2-p53 peptide complex.Conclusion Dihydroartemisinin Ⅰ may serve as an effective MDM2 inhibitor,exerting its effects in the treatment of PLGC by targeting the p53-MDM2 signaling pathway.