近年来，男性患上尿路上皮癌（UC）的发病率较高。本研究旨在探究黄芪多糖（APS）是否能够抑制UC的发展以及其相关的分子机制。我们的数据显示，APS呈剂量依赖性地抑制UC细胞的增殖，并降低RT4和T24细胞的迁移能力。进一步的研究揭示，铁穿透死亡抑制剂铁削酸-1（Fer-1）逆转了APS诱导的细胞死亡、细胞内铁离子（Fe2+）和丙二醛（MDA）累积以及脂质过氧化产物沉积的效应。Western blot和免疫荧光结果显示，APS显著抑制了谷胱甘肽过氧化酶4（GPX4）的表达，但未改变溶质载体家族7成员11 (xCT, SLC7A11)的蛋白水平。进一步分析揭示，APS降低了RT4和T24细胞中xCT的活性。此外，APS显著增加了RT4和T24细胞中蛋白激酶AMP激活型催化亚单位α1（AMPK）和BECN1的磷酸化水平，从而诱导了BECN1-xCT复合物的形成。然而，当在RT4和T24细胞中沉默AMPK时，APS诱导的铁穿透死亡在一定程度上逆转，表明APS介导的铁穿透死亡涉及AMPK信号转导。此外，APS在活体裸鼠中也显示出抑制肿瘤生长的效果。总之，我们的研究首次证明了APS能够通过激活AMPK/BECN1信号通路在UC细胞中促进BECN1-xCT复合物的形成，抑制xCT的活性，降低GPX4的表达，从而诱导铁穿透死亡并最终抑制UC的进展。

In recent years, the incidence of urothelial carcinoma (UC) has been high in men. The aim of this study was to investigate whether astragalus polysaccharide (APS) could inhibit the development of UC and the specific molecular mechanism. Our data showed that APS inhibited the proliferation of UC cells in a dose-dependent manner, and APS reduced the migratory capacity of RT4 and T24 cells. Further studies revealed that the ferroptosis inhibitor ferrostatin-1 (Fer-1) reversed APS-induced cell death, intracellular Fe2+ and malondialdehyde (MDA) accumulation, and lipid peroxidation product deposition. The Western blot and immunofluorescence results showed that APS significantly inhibited the expression of glutathione peroxidase 4 (GPX4) but did not alter the protein level of solute carrier family 7 member 11 (xCT, SLC7A11). Further analysis revealed that APS reduced the activity of xCT in RT4 and T24 cells. Moreover, APS significantly increased the phosphorylation levels of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK) and BECN1 in RT4 and T24 cells, which induced the formation of the BECN1-xCT complex. However, when AMPK was silenced in RT4 and T24 cells, APS-induced ferroptosis was reversed to some extent, indicating that APS-mediated ferroptosis involves AMPK signaling. Moreover, APS has been shown to inhibit tumor growth in nude mice in vivo. In summary, our study demonstrated for the first time that APS could promote the formation of the BECN1-xCT complex in UC cells by activating AMPK/BECN1 signaling, which inhibited the activity of xCT to reduce GPX4 expression, thereby inducing ferroptosis and ultimately inhibiting UC progression.