Oncotarget

Research Papers:

Multiple anti-tumor effects of Reparixin on thyroid cancer

Federica Liotti, Maria De Pizzol, Marcello Allegretti, Nella Prevete and Rosa Marina Melillo _

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Oncotarget. 2017; 8:35946-35961. https://doi.org/10.18632/oncotarget.16412

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Abstract

Federica Liotti1, Maria De Pizzol2, Marcello Allegretti2, Nella Prevete3,4, Rosa Marina Melillo1,4

1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples “Federico II”, Naples, Italy

2Dompé Farmaceutici S.p.A., L’Aquila, Italy

3Dipartimento di Scienze Mediche Traslazionali, University of Naples “Federico II”, Naples, Italy

4Istituto 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.


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