兰州大学学报（医学版）2026，Vol.52Issue(4)：26-33,8.DOI:10.13885/j.issn.2097-681X.M20250941
山柰酚联合二甲双胍治疗结直肠癌的机制研究
Mechanistic study of Kaempferol combined with metformin in the treatment of colorectal cancer
摘要
Abstract
Objective To explore the multi-target synergistic mechanism of Kaempferol combined with met-formin in the treatment of colorectal cancer using network pharmacology,molecular docking,and bioinformat-ics methods,providing a theoretical basis for the discovery of drug combinations with multi-target synergy.Methods The potential targets of Kaempferol and metformin were predicted using databases such as Pub-Chem,SuperPred,and SwissTargetPrediction.These were then intersected with colorectal cancer-related tar-gets obtained from GeneCards,DrugBank and OpenTargets databases.A Protein-Protein Interaction network was constructed using the STRING database to identify key targets.Subsequently,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.Finally,molecular docking and molecular dynamics simulations were conducted to validate the binding characteristics between the drugs and their targets.The UALCAN database was used to analyze the expression differences of core targets in colorectal cancer tissues and their correlation with clinical stages and lymph node metastasis status.Results A total of 65 potential common therapeutic targets of Kaempferol and metformin in treating colorectal cancer were identified,including key targets such as AKT1,ESR1,EGFR,SRC,MMP9,PTGS2,NFKB1,CX-CR4,GSK3B and SIRT1.GO enrichment analysis revealed that these targets were mainly involved in biological processes such as oxidative stress response and cellular response to chemical stress.KEGG pathway enrich-ment analysis indicated its significant involvement in the PI3K-Akt pathway.Molecular docking and dynam-ics simulations demonstrated strong binding affinities between Kaempferol/metformin and targets such as MMP9,SIRT1 and ESR1.UALCAN showed PTGS2,GSK3B and MMP9 were up-regulated and ESR1 was down-regulated in colorectal cancer,correlating with stage and nodal metastasis.Conclusion Kaempferol and metformin may synergistically modulate multiple key targets,including MMP9,SIRT1,and ESR1,as well as the PI3K-Akt pathway,suggesting their potential synergistic effects against colorectal cancer and offering a theoretical reference for multi-target combination interventions in colorectal cancer and for the combined ap-plication of medicine-food homologixl components.关键词
结直肠癌/药食同源/山柰酚/二甲双胍/网络药理学/分子动力学模拟/基质金属蛋白酶-9/PI3K-Akt[信号]通路Key words
colorectal cancer/medicinal-food homology/Kaempferol/metformin/network pharmacology/mo-lecular dynamics simulation/matrix metalloproteinase-9/PI3K-Akt pathway分类
医药卫生引用本文复制引用
徐明丽,郑卿勇,许建国,徐彩花,周泳佳,崔雅婷,朱永红,张馨..山柰酚联合二甲双胍治疗结直肠癌的机制研究[J].兰州大学学报（医学版）,2026,52(4):26-33,8.基金项目
甘肃省科技重大专项-社会发展领域(24ZD17FA003) （24ZD17FA003）
甘肃省高校教师创新基金项目(2025A-402) （2025A-402）
