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• W2603906685 abstract "// Federica Liotti 1 , Maria De Pizzol 2 , Marcello Allegretti 2 , Nella Prevete 3, 4 , Rosa Marina Melillo 1, 4 1 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples “Federico II”, Naples, Italy 2 Dompé Farmaceutici S.p.A., L’Aquila, Italy 3 Dipartimento di Scienze Mediche Traslazionali, University of Naples “Federico II”, Naples, Italy 4 Istituto di Endocrinologia ed Oncologia Sperimentale del CNR “G. Salvatore”, Naples, Italy Correspondence to: Rosa Marina Melillo, email: rosmelil@unina.it Nella Prevete, email: nella.prevete@unina.it Keywords: Reparixin, thyroid cancer, CXCR1, CXCR2 Received: October 19, 2016      Accepted: March 11, 2017      Published: March 21, 2017 ABSTRACT Background: Expression of IL-8 and its receptors CXCR1 and CXCR2 is a common occurrence in human epithelial thyroid cancer (TC). In human TC samples, IL-8 expression is associated with tumor progression. IL-8 enhances proliferation, survival, motility, and leads to the maintenance of stemness features and tumor-initiating ability of TC cells. Here, we studied the effects of Reparixin (formerly Repertaxin), a small molecular weight CXCR1 and CXCR2 inhibitor, on the malignant phenotype of various TC cell lines. Results: Reparixin impaired the viability of epithelial thyroid cancerous cells, but not that of the non-malignant counterpart. Reparixin treatment significantly decreased TC cell survival, proliferation, Epithelial-to-Mesenchymal Transition (EMT) and stemness. CXCR1 and CXCR2 silencing abolished these effects. Reparixin sensitized TC cells to Docetaxel and Doxorubicin in culture. Used as single agent, Reparixin significantly inhibited TC cell tumorigenicity in immunodeficient mice. Finally, Reparixin potentiated the effects of Docetaxel on TC cell xenotransplants in mice. Materials and Methods: We assessed the effects of Reparixin on TC cell viability (by growth curves, BrdU incorporation, TUNEL assay), EMT (by RT-PCR, Flow Cytometry, Migration assays), stemness (by RT-PCR, Flow Cytometry, sphere-formation and self-renewal), and tumorigenicity (by xenotransplantation in nude mice). Conclusions: The present study suggests that Reparixin, both alone and in combination with classic chemotherapics, represents a novel potential therapeutic strategy for aggressive forms of TC." @default.
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• W2603906685 date "2017-03-21" @default.
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• W2603906685 title "Multiple anti-tumor effects of Reparixin on thyroid cancer" @default.
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• W2603906685 doi "https://doi.org/10.18632/oncotarget.16412" @default.
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