Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells.

ABSTRACT: The current study established the first in vitro Encorafenib resistance protocol in BRAF-mutated malignant melanoma (MM) cells and investigated the resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were investigated using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress and iron colorimetric assay. The most resistant group, called A375-R, was determined in the cells treated with a constant dose of 10 nM over 3 months. The viability, apoptosis, and G0/G1 arrest reflected the acquired chemoresistance. Autophagic Beclin and LC3 proteins, and AKT signaling increased in the A375-R. RNA-Seq results also exhibited altered epigenetic regu

SUBMITTER: Colakoglu Bergel C 

PROVIDER: S-EPMC11742906 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature