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Y. 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 | Author(s): Y. 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.