The synergistic effect and mechanism verification of effective components of Biejia-Ezhu against triple-negative breast cancer based on network pharmacology and component compatibility theory
- VernacularTitle:基于网络药理学与组分配伍理论探讨鳖甲-莪术有效组分协同抗三阴性乳腺癌的作用及机制验证
- Author:
Dou-dou FENG
1
;
Xiao-shan LUO
;
Yan-yun MENG
;
Jing-zhe ZHAO
;
Jiu-long ZHU
;
Ya-zhen HUANG
;
Qing XIE
;
Xiang-Li LING
;
Su XIE
Author Information
- Publication Type:Journal Article
- Keywords: Biejia-Ezhu; triple negative breast canc-er; component compatibility; autophagy; mTORC1/ULK1 signaling pathway; effect mechanism
- From: Chinese Pharmacological Bulletin 2025;41(5):950-959
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.
