中国合理用药探索2025，Vol.22Issue(4)：1-11,11.DOI:10.3969/j.issn.2096-3327.2025.04.001
芬苯达唑抗肿瘤谱、潜在分子机制及口服纳米药物研发
Exploring the Antitumor Spectrum and Potential Molecular Mechanisms of Fenbendazole and the Development of its Nanopharmaceuticals
摘要
Abstract
Objective:To elucidate the antitumor spectrum of fenbendazole(FBZ),investigate its therapeutic mechanisms against colon cancer through network pharmacology and molecular docking,and develop an oral nanopharmaceuticals formulation.Methods:The antitumor spectrum of FBZ was evaluated against nine cell lines representing seven common tumor types using CCK-8 assays,colony formation experiments,and flow cytometry.Network pharmacology and molecular docking approaches were then applied to preliminarily identify key molecular targets and signaling pathways involved in FBZ-mediated anti-colon cancer activity.Finally,an oral FBZ nanopharmaceuticals was developed using a bile salt-based delivery system to overcome its poor aqueous solubility.Results:FBZ exerted the strongest inhibitory effect on colorectal cancer cell lines,followed by prostate,lung,liver,ovarian,breast,and pancreatic cancers.Network pharmacology analysis identified six core targets:BRAF,KDR,RAF1,MMP1,MAPK8,and MAPK14.KEGG pathway enrichment revealed significant involvement of the cancer signaling pathway,Rap1 signaling,VEGF signaling,EGFR tyrosine kinase inhibitor resistance,MAPK pathway,Relaxin signaling,and FoxO pathway.Molecular docking demonstrated strong binding affinities of FBZ to MAPK14,BRAF,its mutant form BRAF V600E,and RAF1.The prepared FBZ oral nanopharmaceuticals exhibited a particle size of approximately 300 nm and achieved an aqueous solubility of 0.5 mg/ml-an approximately 500 fold increase over the original drug.Conclusion:FBZ exhibits high sensitivity against colorectal cancer cells in vitro and may inhibit tumor progression through a multi-target and multi-pathway synergistic mechanism.The developed oral nanopharmaceuticals significantly improves its aqueous solubility,providing valuable reference for the potential clinical application of FBZ as an anticancer agent and laying a foundation for future translational research.关键词
芬苯达唑/抗肿瘤/网络药理学/结肠癌/水溶性/纳米药物Key words
fenbendazole/antitumor/network pharmacolgy/colon cancer/water solubility/nanopharmaceuticals分类
药学引用本文复制引用
翟崇凯,杨少哲,张清伟,张贺伟,付秀虹..芬苯达唑抗肿瘤谱、潜在分子机制及口服纳米药物研发[J].中国合理用药探索,2025,22(4):1-11,11.基金项目
河南省生育力保护与优生重点实验室开放课题重点项目(SYLBHYS2022-01) （SYLBHYS2022-01）
