Yuan Donglan, Guo Ting, Zhu Xiaotong, Song Weiwei, Nie Dengyun, Yu Hong
Department of Obstetrics and Gynecology, Affiliated Taizhou People's Hospital of Nanjing University of Traditional Chinese Medicine, Taizhou, 225300, China.
Center for Molecular Medicine, Affiliated Taizhou People's Hospital of Nanjing University of Traditional Chinese Medicine, Taizhou, 225300, China.
J Ovarian Res. 2025 Apr 5;18(1):71. doi: 10.1186/s13048-025-01650-1.
Ovarian cancer (OV) is the leading cause of death among gynecological malignancies. This study aimed to investigate the influence of Icariside II on OV in vitro and in vivo and to elucidate whether Icariside II induces ferroptosis in OV cells by regulating SLC7A11 expression.
SKOV3 cells and OV nude mice were treated with Icariside II, a control-plasmid or an SLC7A11-plasmid. EdU assay, flow cytometry, wound-healing assay, and Transwell assays were used to assess cell proliferation, apoptosis, migration, and invasion respectively. Total iron, Fe levels, and intracellular lipid reactive oxygen species (ROS) stimulation were evaluated in both cells and tissues. Levels of cysteine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) were also analyzed. Ferroptosis markers, including Ptgs2, Chac1, SLC7A11, and apoptosis-associated genes (Bax and Bcl-2), were detected using qRT-PCR, western blotting, and immunohistochemistry (IHC). SLC7A11 expression in OV was explored using data from The Cancer Genome Atlas (TCGA), and validated with IHC staining.
Icariside II-induced ferroptosis in OV cells was confirmed by elevated Fe and total iron levels, enhanced lipid ROS levels, higher Ptgs2 and Chac1 mRNA levels, and reduced levels of SLC7A11, Cys, GSH, and GPX4 in both in vitro and in vivo models. These effects were partially reversed by the SLC7A11-plasmid. Moreover, Icariside II suppressed SKOV3 cell proliferation, inhibited cells migration and invasion, and promoted apoptosis by downregulating SLC7A11 expression. Furthermore, we found that SLC7A11 expression was upregulated in OV tissues compared to adjacent non-tumor tissues.
Icariside II induces ferroptosis in OV by downregulating SLC7A11 expression in vitro and in vivo. Our study identified Icariside II as a promising therapeutic agent for the treatment of OV.
卵巢癌（OV）是妇科恶性肿瘤中导致死亡的主要原因。本研究旨在探讨淫羊藿次苷II在体外和体内对OV的影响，并阐明淫羊藿次苷II是否通过调节SLC7A11表达诱导OV细胞发生铁死亡。
用淫羊藿次苷II、对照质粒或SLC7A11质粒处理SKOV3细胞和OV裸鼠。分别采用EdU检测、流式细胞术、伤口愈合检测和Transwell检测评估细胞增殖、凋亡、迁移和侵袭。对细胞和组织中的总铁、铁水平以及细胞内脂质活性氧（ROS）刺激进行评估。还分析了半胱氨酸（Cys）、谷胱甘肽（GSH）和谷胱甘肽过氧化物酶4（GPX4）的水平。使用qRT-PCR、蛋白质印迹法和免疫组织化学（IHC）检测铁死亡标志物，包括Ptgs2、Chac1、SLC7A11以及凋亡相关基因（Bax和Bcl-2）。利用来自癌症基因组图谱（TCGA）的数据探索OV中SLC7A11的表达，并通过IHC染色进行验证。
在体外和体内模型中，淫羊藿次苷II诱导OV细胞发生铁死亡表现为铁和总铁水平升高、脂质ROS水平增强、Ptgs2和Chac1 mRNA水平升高以及SLC7A11、Cys、GSH和GPX4水平降低。SLC7A11质粒部分逆转了这些作用。此外，淫羊藿次苷II通过下调SLC7A11表达抑制SKOV3细胞增殖、抑制细胞迁移和侵袭并促进凋亡。此外，我们发现与相邻非肿瘤组织相比，OV组织中SLC7A11表达上调。
淫羊藿次苷II在体外和体内通过下调SLC7A11表达诱导OV细胞发生铁死亡。我们的研究确定淫羊藿次苷II是一种有前景的OV治疗药物。
