Astragaloside IV antagonizes the malignant progression of breast cancer induced by macrophage M2 polarization through the TGF-β-regulated Akt/Foxo1 pathway

Astragaloside IV (AS‑IV) was used for breast cancer (BC) treatment in China from ancient times; however, the mechanism of the prevention effect of AS-IV on BC remains not entirely clear. qRT-PCR, western blot and flow cytometry were employed to validate the expression of gene and protein expressions. CCK-8 assay, scratch assay, and transwell assay were used to assess the BC cell proliferation, migration, and invasion. Co-culture of conditional medium from macrophages and BC were performed. AS-IV suppressed macrophage polarized to M2 phenotype and thereby inhibited M2 macrophage-induced BC progression. The inhibitory effect of AS-IV on M2 macrophage polarization was exerted via the deactivation of the Akt/Foxo1 signaling pathway in macrophages by suppressing TGF-β. The addition of TGF-β or the treatment with Akt activator SC79 reversed the regulatory effect of AS-IV on M2 macrophage polarization, which increased M2 macrophage polarization-induced BC cell proliferation, migration and invasion. This present study revealed a new mechanism of AS-IV inhibited M2 macrophage polarization-induced BC progression and may provide a potential target for the treatment of BC. •Astragaloside IV inhibits the polarization of macrophages toward M2 phenotypes and thereby inhibits breast tumor growth.•Astragaloside IV suppresses TGF-β in vitro and in vivo.•The treatment of TGF-β or activation of Akt/Foxo1 reverses the effects of astragaloside IV on breast cancer.