%0 Journal Article
%T Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer.
%A Ochi K
%A Suzawa K
%A Tomida S
%A Shien K
%A Takano J
%A Miyauchi S
%A Takeda T
%A Miura A
%A Araki K
%A Nakata K
%A Yamamoto H
%A Okazaki M
%A Sugimoto S
%A Shien T
%A Yamane M
%A Azuma K
%A Okamoto Y
%A Toyooka S
%J Biochem Biophys Res Commun
%V 529
%N 3
%D 08 2020 27
%M 32736704
%F 3.322
%R 10.1016/j.bbrc.2020.06.077
%X The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.<BR>A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.<BR>TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.<BR>Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.