Abstract
Background Breast cancer poses a significant threat on human health. Rhizoma Dioscoreae (RD), a traditional Chinese medicinal herb, has shown positive effect in breast cancer treatment; however, the underlying molecular mechanisms remain unknown.
Methods We identified the active pharmaceutical ingredients (APIs) in RD and their potential targets using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to breast cancer were gathered from GeneCards and Online Mendelian Inheritance in Man (OMIM) database. We constructed RD API-gene interaction network using Cytoscape software. Protein-protein interaction (PPI) data were obtained from the Search Tool for the Retrieval of Interacting Genes (STRING) database. Key APIs and hub genes were screened via network topological parameters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses were conducted. Molecular docking and in vitro experiments were performed to validate our network pharmacology findings.
Results We identified 12 APIs in RD and 28 genes overlapped between RD and breast cancer. Molecular docking showed stable binding between key ingredients and hub genes. Stigmasterol and diosgenin served as the most critical APIs. Further experimental findings demonstrated that RD inhibited breast cancer via downregulating HIF-1α, RELA, VEGFA, PGR, and NCOA1, critical in tumor angiogenesis and hormone-mediated signaling.
Conclusion RD might inhibit breast cancer angiogenesis and hormone-mediated oncogenesis by downregulating HIF-1α, RELA, VEGFA, PGR, and NCOA1, which provides more evidence for the application of RD in the management of breast cancer.