Bruceine H Mediates EGFR-TKI Drug Persistence in NSCLC by Notch3-Dependent β-Catenin Activating FOXO3a Signaling.

ABSTRACT: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) protein serve as a critical pillar in the treatment of non-small cell lung cancer (NSCLC), but resistance is universal. Identifying the potential key factors of drug resistance to EGFR-TKIs is essential to treat patients with EGFR mutant lung cancer. Our research here shows that bruceine H suppressed the proliferation, migration, and invasion of lung cancer cells; inhibited the growth of human NSCLC cell xenografts; and enhanced the therapeutic effects of gefitinib in the PC-9/GR xenograft models, possibly by inhibiting Notch3. In order to analyze the potential targets of the combination of Notch3 and EGFR-TKIs on resistance to EGFR, we analyzed the differences of gene expression between NSCLC tissues and E

SUBMITTER: Wu J 

PROVIDER: S-EPMC9024338 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature