Breast Cancer Research, Год журнала: 2025, Номер 27(1)

Опубликована: Апрель 23, 2025

The mechanisms underpinning neoadjuvant chemotherapy-induced vascular endothelial injury in breast cancer remain elusive. Our study aims to demonstrate that Neutrophil Extracellular Traps (NETs) play a pivotal role cancer, elucidating upregulation of Solute Carrier 11a1 (Slc11a1) modulates Reactive Oxygen Species (ROS) generation, which may be critical for NETs formation. We investigated the impact chemotherapy on formation and by analyzing dsDNA serum markers patients, cells, mouse models. RNA sequencing neutrophils from models was performed identify potential formation-associated gene Slc11a1, further validated through cellular animal experiments assessing Slc11a1 expression, intracellular ferrous ion content, ROS levels. Knockdown human were also confirm phenotypic results. revealed plasma significantly elevated patients undergoing docetaxel & carboplatin (TCb) chemotherapy, compared controls. In these associated with augmentation markers. Chemotherapy demonstrated TCb treatment markedly injury, can mitigated CI-amidine, protein-arginine deiminase inhibitor. neutrophils, we chemotherapeutic agents (combination carboplatin) induced NETs, subsequently facilitated damage umbilical vein cells vitro. identified as key formation-related gene, upregulated leading increased content generation. its reversal effect TCb-induced upregulation, research underscores capacity augment Slc11a1-mediated is linked injury. elucidates underlying perioperative offering novel insights into therapeutic management strategies patients.

Язык: Английский