@Article{or.2024.050057,
AUTHOR = {LI SUN, SHICHAO ZHUO, XIAOXIN LI, HUSHENG KONG, WEIWEI DU, CHONG ZHOU, JUNXING HUANG},
TITLE = {Astragalus polysaccharide enhances the therapeutic efficacy of cisplatin in triple-negative breast cancer through multiple mechanisms},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {3},
PAGES = {641--651},
URL = {http://www.techscience.com/or/v33n3/59630},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Cisplatin (DDP) has been used in the treatment of various human cancers. However, DDP alone lacks efficacy in treating triple-negative breast cancer (TNBC), and its clinical application is often hampered by side effects. <i>Astragalus polysaccharide</i> (APS) is one of the active components extracted from <i>Astragalus membranaceus</i> and has gained attention for its various biological properties. This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms. <b>Methods:</b> The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8 (CCK8) assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining, wound healing assay, trans-well invasion/migration assay, hematoxylin-eosin (HE) staining, immunohistochemical (IHC) staining, Western Blot (WB) analysis, and fluorescence-activated cell sorting (FACS). An orthotopic model of TNBC was used to assess the <i>in vivo</i> treatment efficacy of single or combination treatment. <b>Results:</b> APS significantly enhanced the anti-proliferative, anti-migratory, and anti-invasive effects of DDP on TNBC cells. The combination of APS and DDP downregulated anti-apoptotic genes (Bcl2 and Bcl-xL) while upregulating pro-apoptotic genes (Puma, Cle-Caspase3, Cle-PARP), leading to enhanced apoptosis. This combination treatment increased E-cadherin levels, decreased Vimentin, Snail, Slug, and Twist levels, and effectively suppressed epithelial-mesenchymal transition (EMT)-associated cell invasion. In the orthotopic model of TNBC, a synergistic reduction in tumor growth was observed in mice treated with APS and DDP. Additionally, the combination of APS and DDP induced the infiltration of CD8<sup>+</sup> T lymphocytes into the tumor immune microenvironment. <b>Conclusion:</b> The combination of APS and DDP exhibits more potent tumor inhibition and anti-tumor immunity than either agent alone, representing a novel approach to enhance therapeutic efficacy without increasing the side effects of DDP.},
DOI = {10.32604/or.2024.050057}
}