Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer

Kosuke Ochi, Ken Suzawa, Shuta Tomida, Kazuhiko Shien, Jui Takano, Shunsaku Miyauchi, Tatsuaki Takeda, Akihiro Miura, Kota Araki, Kentaro Nakata, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Masaomi Yamane, Kazuo Azuma, Yoshiharu Okamoto, Shinichi Toyooka

Research output: Contribution to journalArticle

Abstract

Background: 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. Materials and methods: 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. Results: 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. Conclusion: Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.

Original languageEnglish
Pages (from-to)760-765
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume529
Issue number3
DOIs
Publication statusPublished - Aug 27 2020

Keywords

  • Drug repositioning
  • Drug resistance
  • Epithelial-mesenchymal transition
  • Monensin
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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