2. Academic Validation
  3. Regorafenib promotes ferroptosis in acute myeloid leukemia by upregulating NOX4

Regorafenib promotes ferroptosis in acute myeloid leukemia by upregulating NOX4

  • Biochem Biophys Res Commun. 2025 Dec 15:792:152981. doi: 10.1016/j.bbrc.2025.152981.
Rong Mu 1,  Xintong Pei 2,  Nahua Xu 3,  Baiping Liu 4,  Lubin Liu 5,  Hui Li 6,  Qi Yao 7
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China; Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China; Zunyi Medical University, Zunyi, 563006, China. Electronic address: [email protected].
  • 2 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China. Electronic address: [email protected].
  • 3 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China. Electronic address: [email protected].
  • 4 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China. Electronic address: [email protected].
  • 5 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China. Electronic address: [email protected].
  • 6 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China; Zunyi Medical University, Zunyi, 563006, China. Electronic address: [email protected].
  • 7 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China; Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China. Electronic address: [email protected].
PMID: 41242297 DOI: 10.1016/j.bbrc.2025.152981
Abstract

Acute Myeloid Leukemia (AML) is a challenging hematologic malignancy with limited long-term survival rates. This study explored the role of Regorafenib in promoting Ferroptosis in AML cells through modulation of NOX4 expression. We demonstrated that Regorafenib sensitizes AML cells to Ferroptosis induction both in vitro and in vivo. Mechanistically, Regorafenib treatment upregulated the expression of the NOX4 protein, leading to increased lipid peroxidation. Consistently, NOX4 Inhibitor significantly rescued the Ferroptosis promoting effect of Regorafenib. Importantly, combining Regorafenib with Ferroptosis inducers showed synergistic effect of blocking tumor growth in vivo. This study highlights the potential of Regorafenib as an agent that modulates NOX4 expression, offering new insights into the treatment of AML.

Keywords

AML; Ferroptosis; NOX4; Regorafenib.

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