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Cabergoline reduces cell viability in non functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

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Abstract

Dopamine (DA) therapy of non-functioning pituitary adenomas (NFA) can result in tumor stabilization and shrinkage. However, the mechanism of action is still unknown. Previous evidence showed that DA can inhibit pituitary vascular endothelial growth factor expression (VEGF), that may be involved in pituitary tumor growth. The aim of our study was to clarify whether VEGF secretion modulation might mediate the effects of DA agonists on cell proliferation in human NFA. We assessed DA receptor subtype 2 (DR2) expression in 20 NFA primary cultures, where we also investigated the effects of a selective DR2 agonist, cabergoline (Cab), on VEGF secretion and on cell viability. All NFA samples expressed α-subunit and DR2 was expressed in 11 samples. In DR2 expressing tumors, Cab significantly reduced cell viability (−25%; P < 0.05) and VEGF secretion (−20%; P < 0.05). These effects were counteracted by treatment with the DA antagonist sulpiride. Cab antiproliferative effects were blocked by VEGF. Our data demonstrate that Cab, via DR2, inhibits cell viability also by reducing VEGF secretion in a selected group of NFA, supporting that DA agonists can be useful in the medical therapy of DR2 expressing NFA.

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Acknowledgments

This work was supported by grants from the Italian Ministry of University and Scientific and Technological Research, Fondazione Cassa di Risparmio di Ferrara, Associazione Ferrarese dell’Ipertensione Arteriosa, and Associazione Italiana per la Ricerca sul Cancro (AIRC) in collaboration with Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA) of the University of Ferrara.

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Authors and Affiliations

  1. Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy

    Teresa Gagliano, Carlo Filieri, Mariella Minoia, Mattia Buratto, Federico Tagliati, Maria Rosaria Ambrosio, Ettore degli Uberti & Maria Chiara Zatelli

  2. Neurosurgery Unit, Department of Neuroscience, Azienda Ospedaliero Universitaria, Arcispedale S.Anna, 44121, Ferrara, Italy

    Marcello Lapparelli

  3. Department of Neurosurgery, Ospedale Maggiore-Bellaria, Bologna, Italy

    Matteo Zoli & Giorgio Frank

  4. Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA), University of Ferrara, Ferrara, Italy

    Ettore degli Uberti & Maria Chiara Zatelli

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  1. Teresa Gagliano
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Correspondence to Maria Chiara Zatelli.

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Gagliano, T., Filieri, C., Minoia, M. et al. Cabergoline reduces cell viability in non functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Pituitary 16, 91–100 (2013). https://doi.org/10.1007/s11102-012-0380-1

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