Targeting FBXL5 to induce ferroptosis and reverse oxaliplatin resistance in iron-rich colorectal cancer
Year: 2025
Type: article
Abstract: Oxaliplatin resistance remains a major challenge in colorectal cancer (CRC) treatment. We investigated the FBXL5/IREB2/TFRC axis in ferroptosis-mediated resistance reversal. Bioinformatics analysis identified IREB2 as co-expressed in oxaliplatin resistance and ferroptosis pathways. Clinical samples revealed elevated iron metabolism in resistant CRC tissues. In vitro, FBXL5 knockdown in oxaliplatin-resistant cells (HCT-116/OXA) upregulated IREB2/TFRC, increased Fe²⁺/MDA, and reduced viability/proliferation. Combining oxaliplatin with ferroptosis inducer Erastin enhanced cell death, reversed by ferroptosis inhibitor Ferrostatin-1. Our findings demonstrate that targeting FBXL5 disrupts iron homeostasis, triggers ferroptosis, and overcomes oxaliplatin resistance in CRC.
Source: Scientific Reports
Authors: Miaomiao Wang, Ruizhe Zhang, Shuang He, Feifei Wen, Xiaojie Yu, Xiaoyang Xu, Yangyang Li, Shuhua Wu
Institution: Binzhou Medical University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Award: G4427583389
OpenAlex ID: W4415500058