Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-κB Signaling Pathway.

ABSTRACT: Background: The major limitation of EGFR TKIs in EGFR-mutant lung cancer therapy is the development of acquired resistance. The underlying mechanisms remain unknown in about 30% of cases. NF-κB activation was encountered in the acquired resistance to EGFR TKIs. Unfortunately, none of NF-κB inhibitors has been clinically approved. The most commonly used antidiabetic drug metformin has demonstrated antitumor effects associated with NF-κB inhibition. Therefore, in this study, metformin was examined for its antitumor and antiresistance effects and underlying mechanisms. Methods: In vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to EGFR TKIs were used. Results: We found that NF-κB was activated in EGFR-mutant lung cancer cells with a

SUBMITTER: Li L 

PROVIDER: S-EPMC7511631 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature