Network pharmacology analysis revealed novel target genes of Astragaloside IV in breast cancer and breast cancer stem cells

Objective: Breast cancer is one of the most common malignant tumors in women and a leading cause of cancer death in women. Astragaloside IV (AS-IV) has been extensively shown to possess various pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor and immune-regulatory effects. However, the target genes of AS-IV for breast cancer and breast cancer stem cells (BCSCs), and underlying mechanisms remain unknown. Our investigation focused on investigating the potential hub genes of AS-IV in breast cancer and BCSCs, focusing specifically on the underlying signaling pathways. Methods: In this study, we employed the network pharmacology to identify the hub genes targeted by AS-IV in breast cancer and BCSCs. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to investigate the underlying mechanism of AS-IV treatment. Finally, a comprehensive interaction network was constructed to demonstrate the relationships among AS-IV, BCSCs, breast cancer, KEGG pathways, GO terms, and hub genes. Results: A total of 20 shared genes were identified, from which 10 hub genes were selected: catenin beta 1 (CTNNB1), Jun proto-oncogene (JUN), signal transducer and activator of transcription 3 (STAT3), glycogen synthase kinase 3 beta (GSK3B), AKT serine/threonine kinase 1 (AKT1), phosphatase and tensin homolog (PTEN), epidermal growth factor (EGF), interleukin 6 (IL6), hypoxia inducible factor 1 subunit alpha (HIF1A), tumor necrosis factor (TNF). Enrichment analyses revealed their involvement in key pathways, including PD1 and PDL1 checkpoint pathway in cancer, EGFR tyrosine kinase inhibitor resistance and so on, which regulate cancer cell proliferation, survival, metastasis, and immune evasion. The interaction network highlighted the pivotal roles of these hub genes in oncogenic and immunological processes. Conclusion: AS-IV demonstrated therapeutic potential against breast cancer and BCSCs by targeting critical hub genes and modulating multiple oncogenic signaling pathways. These findings provide novel insights into the molecular mechanisms of AS-IV, offering potential targets for overcoming anti-estrogen therapy resistance and advancing breast cancer treatment.