Inhibition of BRD4 sensitizes NSCLC cells to osimertinib by suppressing APT1 and promoting MST1 palmitoylation.

ABSTRACT: Osimertinib is widely used to treat non-small-cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations. However, osimertinib resistance inevitably develops in almost all patients. In our study, osimertinib-resistant HCC827/OR and PC-9/OR cells were established from parental osimertinib-sensitive cells, and osimertinib (AZD9291) and NHWD870, a bromodomain and extra-terminal (BET) inhibitor, were used to treat cells and mice. PC-9/OR and HCC827/OR cells were subcutaneously injected into mice to establish a mouse model of NSCLC. Luciferase, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assays were applied to analyze transcription factors (TFs) binding to the APT1 promoter. MST1 palmitoylation was examined with acyl resin-assis

SUBMITTER: Wang S 

PROVIDER: S-EPMC12583557 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature