2. Academic Validation
  3. Ferroptotic resistance involved in PTEN-loss prostate cancer progression

Ferroptotic resistance involved in PTEN-loss prostate cancer progression

  • Discov Oncol. 2025 Nov 25;16(1):2166. doi: 10.1007/s12672-025-03990-2.
Yaoyao Jing 1 2,  Donghui Xing 3,  Zhigang Zhao 4,  Xiaofang Wang 5
Affiliations

Affiliations

  • 1 Department of Day ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
  • 2 Department of Medical Oncology, Tianjin First Central Hospital, School of Medicine. Nankai University, Tianjin, 300192, China.
  • 3 Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
  • 4 Department of Medical Oncology, Tianjin First Central Hospital, School of Medicine. Nankai University, Tianjin, 300192, China. [email protected].
  • 5 Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. [email protected].
PMID: 41288888 DOI: 10.1007/s12672-025-03990-2
Abstract

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.

Keywords

Ferroptosis; GPX4; PTEN; Prostate cancer.

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