Mechanisms of kaempferol against colorectal cancer based on network pharmacology and cellular experiments
10.7659/j.issn.1005-6947.250213
- VernacularTitle:基于网络药理学与细胞实验的山柰酚抗结直肠癌作用机制研究
- Author:
Furui ZHONG
1
;
Hua YANG
1
Author Information
1. 四川省自贡市第四人民医院 普通外科,四川 自贡 643000
- Publication Type:Journal Article
- Keywords:
Colorectal Neoplasms;
Kaempferols;
Network Pharmacology;
Cell Proliferation;
Apoptosis;
Neoplasm Invasiveness
- From:
Chinese Journal of General Surgery
2025;34(10):2180-2190
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:Colorectal cancer(CRC)has a high incidence and mortality rate,and the effectiveness of current therapies for advanced cases remains limited.Kaempferol,a natural flavonoid compound,exhibits antioxidant,anti-inflammatory,and antitumor properties.This study aimed to elucidate the key molecular targets and underlying mechanisms of kaempferol against CRC through an integrated approach combining network pharmacology and experimental validation.Methods:Potential targets of kaempferol were identified via SwissTargetPrediction,SEA,PharmMapper,and TargetNet databases,and CRC-related targets were retrieved from GeneCards,OMIM,CTD,and DrugBank.The intersection targets were used to construct a compound-target-disease network.Protein-protein interaction(PPI)analysis using the STRING database and Cytoscape software identified core targets,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.In vitro experiments with human CRC HCT-116 cells evaluated cell proliferation(CCK-8 assay),colony formation,migration(scratch assay),invasion(Transwell assay),and expression of apoptosis-and cell cycle-related proteins(Western blot).Results:A total of 492 kaempferol targets and 5 078 CRC-related targets were obtained,with 269 overlapping targets identified as potential therapeutic candidates.PPI network analysis revealed 53 core targets,including Akt1,HSP90AA1,ESR1,SRC,CASP3,and NFKB1.GO analysis indicated enrichment in cellular stress response,apoptosis regulation,and oxidative stress processes;KEGG pathways were primarily related to chemical carcinogenesis-receptor activation,prolactin,estrogen,and PI3K/Akt signaling.Experimental validation demonstrated that kaempferol markedly inhibited HCT-116 cell proliferation,colony formation,migration,and invasion in a dose-dependent manner(all P<0.05),accompanied by downregulation of Bcl-2 and cyclin D1 and upregulation of Bax(all P<0.05).Conclusion:Kaempferol exerts anti-CRC effects through multi-target and multi-pathway mechanisms,including inhibition of proliferation,migration,and invasion,and induction of apoptosis,potentially via modulation of the PI3K/Akt and estrogen signaling pathways.These findings provide theoretical and experimental evidence supporting kaempferol as a promising candidate for CRC therapy.
