2. Academic Validation
  3. Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway

Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway

  • Cell Death Dis. 2023 Feb 23;14(2):151. doi: 10.1038/s41419-023-05664-9.
Jin-Feng Zhu 1 2,  Yi Liu 3,  Wen-Ting Li 4,  Ming-Hui Li 5,  Chao-Hui Zhen 1,  Pei-Wei Sun 1,  Ji-Xin Chen 1,  Wen-Hao Wu 1,  Wei Zeng 6
Affiliations

Affiliations

  • 1 Department of General Surgery, Shenzhen University General Hospital, 518055, Shenzhen, Guangdong Province, P.R. China.
  • 2 Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, Guangdong Province, P.R. China.
  • 3 Department of Cardiothoracic Surgery, Shenzhen University General Hospital, 518055, Shenzhen, Guangdong Province, P.R. China.
  • 4 Department of Pathology, Shenzhen University General Hospital, 518055, Shenzhen, Guangdong Province, P.R. China.
  • 5 Department of Ultrasound, Shenzhen University General Hospital, 518055, Shenzhen, Guangdong Province, P.R. China.
  • 6 Department of Oncology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), 1 Jiazi Road, 528000, Foshan, Guangdong Province, P.R. China. zengwei1119@163.com.
PMID: 36823108 DOI: 10.1038/s41419-023-05664-9
Abstract

Ibrutinib is a drug that inhibits the protein Burton's tyrosine kinase and thereby the nuclear translocation of Nrf2, which played a key role in mediating the activation of Antioxidants during stress conditions and Ferroptosis resistance. This study aimed to identify the effect of Ibrutinib and Ferroptosis inducer on colorectal Cancer (CRC) treatment and its underlying mechanism. In our study, we found the upregulation of Nrf2 was correlated with CRC progression and antioxidant proteins. Ibrutinib sensitized CRC to Ferroptosis inducers, suggested by further reduced CRC cell viability, proliferation and decreased antioxidant protein levels in CRC cells after combination treatment of Ibrutinib and RSL3 or Ibrutinib and Erastin both in vivo and in vitro. Knockout of Nrf2 diminished the regulatory effect of Ibrutinib on CRC sensitivity to Ferroptosis inducers. Altogether, this study demonstrated that Ibrutinib increases the sensitivity of CRC cell to Ferroptosis inducers by inhibiting Nrf2.

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