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S. Lee



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      220P - Effects of pifithrin-μ on the growth of acidity-tolerant malignant mesothelioma cells and epithelial-mesenchymal transition (ID 264)

      12:50 - 12:50  |  Presenting Author(s): S. Lee

      • Abstract

      Background:
      Heat shock protein 70, which protects cells from various forms of cellular stress, has gained significant attention as a potential therapeutic target in various malignancies.

      Methods:
      Here, pifithrin-μ, an effective dual inhibitor of HSP70 and p53, was employed to examine its anticancer activities and to analyze its possible effect for epithelial-mesenchymal transition (EMT) in malignant mesothelioma cells.

      Results:
      MSTO-211HAcT cells, pre-adapted in medium containing lactic acid, showed more resistance to anticancer drugs, cisplatin and gemcitabine, when compared with their parental acid-sensitive MSTO-211H cells. Pifithrin-μ treatment induced cell death in a p53-independent manner and developed EMT-like phenomenon, which was characterized by an elongated cell morphology, a decrease in the levels of epithelial cell markers, including E-cadherin, claudin 1 and b-catenin, and an increase in the level of mesenchymal markers, including vimentin and Snail, and increased migratory and invasive properties in MSTO-211HAcT cells. Moreover, p53 knockdown significantly enhanced the pifithrin-μ-mediated changes of critical EMT markers, migration and invasion, and anoikis resistance.

      Conclusions:
      Collectively, pifithrin-μ may contribute to malignant progression by promoting the EMT, at least in part, through the p53 inhibition, despite its preferential growth-inhibiting and apoptosis-promoting effects on MSTO-211HAcT cells under acidic extracellular environment.

      Clinical trial identification:


      Legal entity responsible for the study:
      Soonchunhyang University

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.