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
- Author:
Qiao CHU
1
;
Xiaona WANG
2
;
Jiaying XU
3
;
Huilin PENG
3
;
Yulin ZHAO
3
;
Jing ZHANG
3
;
Guoyu LU
1
;
Kai WANG
3
Author Information
1. Department of Emergency Internal Medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
2. Department of Plastic Surgery, Bengbu First People's Hospital, Bengbu 233000, China.
3. Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China.
- Publication Type:Journal Article
- Keywords:
Pulsatilla saponin D;
invasion;
metastasis;
molecular docking;
network pharmacology;
triple negative breast cancer
- MeSH:
Humans;
Triple Negative Breast Neoplasms/metabolism*;
Saponins/pharmacology*;
Pulsatilla/chemistry*;
Female;
Molecular Docking Simulation;
Cell Line, Tumor;
Neoplasm Invasiveness;
Protein Interaction Maps;
Neoplasm Metastasis;
Signal Transduction/drug effects*;
Cell Movement/drug effects*
- From:
Journal of Southern Medical University
2025;45(1):150-161
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS:The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
