Pulsatilla saponin D inhibits invasion and metastasis of triple-negative breast cancer cells through multiple targets and pathways
10.12122/j.issn.1673-4254.2025.01.18
- VernacularTitle:白头翁皂苷D通过多靶点和多途径抑制三阴性乳腺癌侵袭转移
- Author:
Qiao CHU
1
;
Xiaona WANG
;
Jiaying XU
;
Huilin PENG
;
Yulin ZHAO
;
Jing ZHANG
;
Guoyu LU
;
Kai WANG
Author Information
1. 蚌埠医科大学第一附属医院急诊内科,安徽 蚌埠 233004
- Publication Type:Journal Article
- Keywords:
Pulsatilla saponin D;
network pharmacology;
molecular docking;
triple negative breast cancer;
invasion;
metastasis
- From:
Journal of Southern Medical University
2025;45(1):150-161
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism by which Pulsatilla saponin D(PSD)inhibits invasion and metastasis of triple-negative breast cancer(TNBC).Methods The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC.The"PSD-target-disease"interaction network was constructed and protein-protein interaction(PPI)analysis was performed to obtain the core targets,which were analyzed for KEGG pathway and GO functional enrichment.Molecular docking study of the core targets and PSD was performed,and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells.Results Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets.GO analysis yielded 175 entries related to the binding of biomolecules(protein,DNA and RNA),enzyme activities,and regulation of gene transcription.KEGG analysis yielded 46 entries involving pathways in cancer,chemical carcinogenesis-receptor activation,microRNAs in cancer,chemical carcinogenesis-reactive oxygen species,PD-L1 expression and PD-1 checkpoint pathway in cancer.Molecular docking showed high binding affinities of PSD to MTOR,HDAC2,ABL1,CDK1,TLR4,TERT,PIK3R1,NFE2L2 and PTPN1.In cultured TNBC cells,treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2,MMP9,N-cadherin and the core proteins p-mTOR,ABL1,TERT,PTPN1,HDAC2,PIK3R1,CDK1,TLR4 as well as NFE2L2 expressionin the cell nuclei.Conclusion The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
