摘要
Background:Triple-negative breast cancer(TNBC)has long been a difficult therapeutic target to overcome because of its extreme aggressiveness,poor efficacy and rarity of available treatment regimens.To explore the anti-TNBC potential of Caulis Polygoni Multiflori(CPM),this investigation applied an integrated computational and experimental approach.Methods:Bioactive CPM compounds were investigated via screening of three TCM databases(TCMSP,TCMID,and HERB)using Bioavailability(OB≥30%)as inclusion criteria.TNBC targets were obtained from the online resources GeneCards,CTD,and OMIM network pharmacology analysis was used to determine common target(s),utilizing two PPI analysis tools–STRING and Cytoscape.Molecular docking assessed target-compound interactions by means of AutoDock Vina.In vitro studies conducted on MDA-MB-231 cells involved evaluating inhibitory effects via MTT,wound-healing assay,transwell,and qPCR techniques.Results:Six bioactive compounds were identified,with emodin(IC_(50) approximately 15μM)and chrysophanol(IC50 approximately 25μM)showing strong binding to TNBC targets(emodin-HSP90AB1:−9.42 kcal/mol;chrysophanol-SRC:−8.32 kcal/mol).Network analysis revealed 143 shared targets,with BCL2,EGFR and ESR1 as key nodes.Pathway analysis implicated PI3K-AKT signaling and apoptosis.In vitro,emodin and chrysophanol synergistically inhibited proliferation,migration and invasion,while downregulating BCL2,EGFR and ESR1 expression.Conclusion:To the best of our knowledge,this is the first report that describes the synergistic mechanisms of multiple compounds from the extract of CPM in TNBC with chrysophanol and emodin working as the main components by mediating oncogenic pathways.
基金
supported by 2022 Anhui University Research Project(grant numbers No.2022AH051162)
2023 Anhui University Collaborative innovation project(grant numbers No.GXXT-2023-074)
National Key Clinical Collaboration Project for Difficult and Complex Diseases(Ovarian Malignancies)Integrating Traditional Chinese and Western Medicine(grant numbers National Traditional Chinese Medicine Comprehensive Development Document(2024)No.3).
