The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology, China.
Baotou Medical College of Inner Mongolia University of Science and Technology, China.
Pathol Res Pract. 2023 Sep;249:154766. doi: 10.1016/j.prp.2023.154766. Epub 2023 Aug 14.
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.
从古代开始，黄芪甲苷（AS-IV）就被用于治疗乳腺癌（BC）；然而，AS-IV 预防 BC 的作用机制尚不完全清楚。
采用 qRT-PCR、western blot 和流式细胞术验证基因和蛋白表达。用 CCK-8 检测、划痕实验和 Transwell 检测评估 BC 细胞增殖、迁移和侵袭。进行巨噬细胞条件培养基与 BC 的共培养。
AS-IV 抑制巨噬细胞向 M2 表型极化，从而抑制 M2 巨噬细胞诱导的 BC 进展。AS-IV 对 M2 巨噬细胞极化的抑制作用是通过抑制 TGF-β来激活巨噬细胞中的 Akt/Foxo1 信号通路来发挥的。添加 TGF-β或用 Akt 激活剂 SC79 处理可逆转 AS-IV 对 M2 巨噬细胞极化的调节作用，从而增加 M2 巨噬细胞极化诱导的 BC 细胞增殖、迁移和侵袭。
本研究揭示了 AS-IV 抑制 M2 巨噬细胞极化诱导的 BC 进展的新机制，可为 BC 的治疗提供潜在靶点。
