title: Cabergoline reduces cell viability in non functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion.
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.
authors.affiliation: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100, Ferrara, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gagliano
authors.forename: Carlo
authors.initials: C
authors.lastname: Filieri
authors.forename: Mariella
authors.initials: M
authors.lastname: Minoia
authors.forename: Mattia
authors.initials: M
authors.lastname: Buratto
authors.forename: Federico
authors.initials: F
authors.lastname: Tagliati
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: Marcello
authors.initials: M
authors.lastname: Lapparelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Zoli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Frank
authors.forename: Ettore
authors.initials: E
authors.lastname: degli Uberti
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
mesh_terms: D000368:Aged; D000077465:Cabergoline; D002470:Cell Survival / Q000187:drug effects*; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004873:Ergolines; D011954:Receptors, Dopamine; D042461:Vascular Endothelial Growth Factor A; D000077465:Cabergoline