药学研究2025，Vol.44Issue(4)：320-327,8.DOI:10.13506/j.cnki.jpr.2025.04.002
二氢丹参酮Ⅰ治疗胃癌前病变的药效及作用机制
Efficacy and mechanism of dihydrotanshinone Ⅰ in the treatment of precancerous lesions of gastric cancer
摘要
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.关键词
二氢丹参酮Ⅰ/胃癌前病变/p53/鼠双微体2Key words
Dihydrotanshinone Ⅰ/Precancerous lesions of gastric cancer/p53/MDM2分类
中医学引用本文复制引用
孟祥梅,褚福浩,郑浩呈,陈洁娜,林洁,李涛,丁霞..二氢丹参酮Ⅰ治疗胃癌前病变的药效及作用机制[J].药学研究,2025,44(4):320-327,8.基金项目
国家自然科学基金面上项目(No.81903792) （No.81903792）
国家自然科学基金青年科学基金项目(No.82305179、82204894) （No.82305179、82204894）
国家博士后科学基金资助项目(No.2019M650600) （No.2019M650600）
