Scholarlink

<p>Ferroptosis and immune evasion are pivotal mechanisms in the pathogenesis of breast cancer (BC), making them promising therapeutic targets. Phillygenin (PHI), a lignan compound derived from <i>Forsythiae Fructus</i>, has demonstrated broad pharmacological properties, including anti-tumor effects. To discuss the impact of PHI on BC. The study examined PHI’s anti-tumor properties and mechanisms using CCK-8 assays, biochemical analyses, DCHF-DA staining, ELISA, immunofluorescence, and western blot techniques. Tumor-bearing mice were utilized for studies in vivo, with tumor tissues being analyzed by H&amp;E staining, immunohistochemistry, and western blotting. The viability of MDA-MB-231 and MCF7 cells was notably repressed by PHI, with respective IC50 values of 81.44 µM and 95.72 µM. PHI elevated intracellular Fe<sup>2+</sup> levels, an effect synergistically enhanced by erastin but attenuated by ferrostatin-1. Furthermore, PHI increased reactive oxygen species (ROS) levels while downregulating GPX4 and SLC7A11 expression in both cell lines. PHI also enhanced CD8<sup>+</sup> T cell cytotoxicity and upregulated IFN-γ and IL-2 levels, but suppressing PD-L1 expression. Mechanistically, PHI repressed the phosphorylation of AKT and GSK3β, along with the β-catenin expression, effects that were reversed by the AKT activator SC79. SC79 also counteracted PHI-induced changes in proliferation, ferroptosis, and immune evasion markers in MDA-MB-231 cells. PHI decreased tumor size and mass, lowered GPX4, p-AKT/AKT, p-GSK3β/GSK3β, and β-catenin levels, and elevated IFN-γ levels in MDA-MB-231 xenograft models. PHI inhibited BC cell proliferation and immune evasion while promoting ferroptosis through suppression of the AKT/β-catenin axis, highlighting its possible as a therapeutic agent for BC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Decoding phillygenin’s dual attack on breast cancer: ferroptosis induction and immune evasion suppression

  • 期刊论文

  • 发表日期：

    2025年7月22日

查看全文
  • Yan Zhang,
  • Xiaohong Lu,
  • Ruie Li,
  • Jingheng Zhang,
  • Jiayu Peng,
  • Yafei Li

摘要

Ferroptosis and immune evasion are pivotal mechanisms in the pathogenesis of breast cancer (BC), making them promising therapeutic targets. Phillygenin (PHI), a lignan compound derived from Forsythiae Fructus, has demonstrated broad pharmacological properties, including anti-tumor effects. To discuss the impact of PHI on BC. The study examined PHI’s anti-tumor properties and mechanisms using CCK-8 assays, biochemical analyses, DCHF-DA staining, ELISA, immunofluorescence, and western blot techniques. Tumor-bearing mice were utilized for studies in vivo, with tumor tissues being analyzed by H&E staining, immunohistochemistry, and western blotting. The viability of MDA-MB-231 and MCF7 cells was notably repressed by PHI, with respective IC50 values of 81.44 µM and 95.72 µM. PHI elevated intracellular Fe2+ levels, an effect synergistically enhanced by erastin but attenuated by ferrostatin-1. Furthermore, PHI increased reactive oxygen species (ROS) levels while downregulating GPX4 and SLC7A11 expression in both cell lines. PHI also enhanced CD8+ T cell cytotoxicity and upregulated IFN-γ and IL-2 levels, but suppressing PD-L1 expression. Mechanistically, PHI repressed the phosphorylation of AKT and GSK3β, along with the β-catenin expression, effects that were reversed by the AKT activator SC79. SC79 also counteracted PHI-induced changes in proliferation, ferroptosis, and immune evasion markers in MDA-MB-231 cells. PHI decreased tumor size and mass, lowered GPX4, p-AKT/AKT, p-GSK3β/GSK3β, and β-catenin levels, and elevated IFN-γ levels in MDA-MB-231 xenograft models. PHI inhibited BC cell proliferation and immune evasion while promoting ferroptosis through suppression of the AKT/β-catenin axis, highlighting its possible as a therapeutic agent for BC.