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<p>Ferroptosis, a newly recognized form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a pivotal role in cancer development. Herein, we investigated the mechanisms of ferroptotic resistance mediated by Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in prostate cancer cells. The ferroptosis inducer Erastin was used to evaluate the effects on cell viability, colony formation, and Reactive Oxygen Species (ROS) level in three prostate cancer cell lines: PTEN wild-type (DU145 cells) and two of the PTEN null cells (PC3 and LNCaP cells). DU145 cells were prone to ferroptosis, whereas PC3 and LNCaP cells exhibited reduced sensitivity to Erastin-induced ferroptosis. Mechanistically, PTEN loss increased Glutathione peroxidase 4 (GPX4) expression and subsequently decreased intracellular ROS level, which was associated with elevated GPX4 mRNA levels. Knockdown of GPX4 by RNAi reversed the resistance of PTEN-deficient PC3 and LNCaP cells to Erastin. Collectively, our findings suggest that ferroptosis can serve as a potential therapeutic strategy for prostate cancer, and PTEN status may influence cellular sensitivity to ferroptosis.</p>

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Ferroptotic resistance involved in PTEN-loss prostate cancer progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Yaoyao Jing,
  • Donghui Xing,
  • Zhigang Zhao,
  • Xiaofang Wang

摘要

Ferroptosis, a newly recognized form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a pivotal role in cancer development. Herein, we investigated the mechanisms of ferroptotic resistance mediated by Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in prostate cancer cells. The ferroptosis inducer Erastin was used to evaluate the effects on cell viability, colony formation, and Reactive Oxygen Species (ROS) level in three prostate cancer cell lines: PTEN wild-type (DU145 cells) and two of the PTEN null cells (PC3 and LNCaP cells). DU145 cells were prone to ferroptosis, whereas PC3 and LNCaP cells exhibited reduced sensitivity to Erastin-induced ferroptosis. Mechanistically, PTEN loss increased Glutathione peroxidase 4 (GPX4) expression and subsequently decreased intracellular ROS level, which was associated with elevated GPX4 mRNA levels. Knockdown of GPX4 by RNAi reversed the resistance of PTEN-deficient PC3 and LNCaP cells to Erastin. Collectively, our findings suggest that ferroptosis can serve as a potential therapeutic strategy for prostate cancer, and PTEN status may influence cellular sensitivity to ferroptosis.