221P Treatment experience of pleural malignant mesothelioma in a tertiary referral center in Mexico

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 epithelialmesenchymal 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 p53independent 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-μmediated 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.