卵巢癌干细胞 (OCSC) 显着影响 OC 的预后、化疗耐药性和治疗结果。虽然铁死亡已被证明对 OCSC 有效，但铁死亡和 OCSC 之间复杂的关系仍不完全清楚。在这里，我们通过乳腺球培养富集了卵巢癌干样细胞（OCSLC），作为 OCSC 模型。与非干 OC 细胞相比，OCSLC 表现出较高的铁死亡易感性，这与 FXN 水平升高相关。 FXN 最近已成为铁死亡的潜在调节剂。 FXN 敲低降低了干性标记 nanog、球形形成能力、增加了活性氧 (ROS) 的产生并减弱了 OCSLC 的活力。 FXN 过表达加剧了铁死亡抵抗并减少了 RSL3 诱导的细胞死亡。 FXN 敲低阻碍了 OCSLC 异种移植肿瘤的生长，并加剧了过氧化还原蛋白 3 (PRDX3) 的退化，过氧化还原蛋白 3 是一种参与氧化应激的线粒体抗氧化蛋白。因此，OCSLC 中 FXN 升高会抑制 ROS 积累，促进铁死亡抵抗，并调节抗氧化蛋白 PRDX3。 FXN 成为 OC 的潜在治疗靶点。© 2024 作者。

Ovarian cancer stem cells (OCSCs) significantly impact the prognosis, chemoresistance, and treatment outcomes in OC. While ferroptosis has been proven effective against OCSCs, the intricate relationship between ferroptosis and OCSCs remains incompletely understood. Here, we enriched ovarian cancer stem-like cells (OCSLCs) through mammosphere culture, as an OCSC model. OCSLCs displayed heightened ferroptosis susceptibility, correlating with elevated FXN levels compared to non-stem OC cells. FXN has recently emerged as a potential regulator in ferroptosis. FXN knockdown diminished stemness marker nanog, sphere-forming ability, increased reactive oxygen species (ROS) generation, and attenuated OCSLCs viability. FXN overexpression exacerbated ferroptosis resistance and reduced RSL3-induced cell death. FXN knockdown impeded OCSLC xenograft tumor growth and exacerbated the degeneration of peroxiredoxin 3 (PRDX3), a mitochondrial antioxidant protein participates in oxidative stress. Thus, elevated FXN in OCSLCs suppresses ROS accumulation, fostering ferroptosis resistance, and regulates the antioxidant protein PRDX3. FXN emerges as a potential therapeutic target for OC.© 2024 The Authors.