卵巢癌仍然是一种常见的妇科肿瘤，也是全球第五大死亡原因。基于紫杉醇的化疗是治疗卵巢癌的标准方法。谷胱甘肽过氧化物酶 4 (GPX4) 是铁死亡的关键调节因子，铁死亡是细胞死亡的一种重要形式。在这里，我们研究了GPX4抑制介导的铁死亡对卵巢癌细胞对紫杉醇敏感性的影响。建立了A2780/PTX和OVCAR-3/PTX紫杉醇耐药的卵巢癌细胞，并通过慢病毒产生了稳定的GPX4敲除细胞系GPX4-sgRNA。分析GPX4表达水平、凋亡率和细胞活力。测量铁死亡相关因子指标如丙二醛（MDA）和活性氧（ROS）的水平。结果表明，紫杉醇耐药细胞中GPX4蛋白和mRNA水平升高。此外，GPX4敲除降低了细胞活力并抑制了集落形成率。此外，我们发现 GPX4 抑制通过诱导铁死亡来增加紫杉醇敏感性。总之，我们的研究表明，GPX4 抑制可促进铁死亡并增加体外卵巢癌细胞对紫杉醇的敏感性。© 2023。作者，独家Springer Nature B.V. 的许可

Ovarian cancer remains a common gynecological tumor and the fifth leading cause of death worldwide. Taxol-based chemotherapy is a standard approach to the treatment of ovarian cancer. Glutathione peroxidase 4 (GPX4) is the key regulator of ferroptosis, which is an important form of cell death. Here, we investigate the effect of GPX4 inhibition-mediated ferroptosis on the sensitivity of ovarian cancer cells to Taxol.A2780/PTX and OVCAR-3/PTX Taxol-resistant ovarian cancer cells were established, and stable GPX4 knockout cell lines were generated via lentivirus GPX4-sgRNA. The GPX4 expression level, the apoptosis rate and cell viability were analyzed. The levels of ferroptosis-related factor indicators such as malondialdehyde (MDA) and reactive oxygen species (ROS) were measured. The results showed that the GPX4 protein and mRNA levels were increased in the Taxol-resistant cells. Moreover, GPX4 knockout reduced cell viability and inhibited the colony formation rate. In addition, we found that GPX4 inhibition increased Taxol sensitivity by inducing ferroptosis.In summary, our studies reveal that GPX4 inhibition promotes ferroptosis and increases the sensitivity of ovarian cancer cells to Taxol in vitro.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.