Vazquez-Borrego, Mari CL-Lopez, FernandoGalvez-Moreno, Maria AFuentes-Fayos, Antonio CVenegas-Moreno, EvaHerrera-Martinez, Aura DBlanco-Acevedo, CristóbalSolivera, JuanLandsman, TanyaGahete, Manuel DSoto-Moreno, AlfonsoCuller, Michael DCastaño, Justo PLuque, Raul M2023-01-252023-01-252019-05-19Vázquez-Borrego MC, L-López F, Gálvez-Moreno MA, Fuentes-Fayos AC, Venegas-Moreno E, Herrera-Martínez AD, et al. A New Generation Somatostatin-Dopamine Analogue Exerts Potent Antitumoral Actions on Pituitary Neuroendocrine Tumor Cells. Neuroendocrinology. 2020;110(1-2):70-82http://hdl.handle.net/10668/14215Pituitary neuroendocrine tumors (PitNETs) represent approximately 15% of all intracranial tumors and usually are associated with severe comorbidities. Unfortunately, a relevant number of patients do not respond to currently available pharmacological treatments, that is, somatostatin analogs (SSAs) or dopamine-agonists (DA). Thus, novel, chimeric somatostatin/dopamine compounds (dopastatins) that could improve medical treatment of PitNETs have been designed. This study aims to determine the direct therapeutic effects of a new-generation dopastatin, BIM-065, on primary cell cultures from different PitNETs subtypes. Thirty-one PitNET-derived cell cultures (9 corticotropinomas, 9 somatotropinomas, 11 nonfunctioning pituitary adenomas [NFPAs], and 2 prolactinomas), were treated with BIM-065, and key functional endpoints were assessed (cell viability, apoptosis, hormone secretion, expression levels of key genes, free cytosolic [Ca2+]i dynamics, etc.). AtT-20 cell line was used to evaluate signaling pathways in response to BIM-065. This chimeric compound decreased cell viability in all corticotropinomas and somatotropinomas tested, but not in NFPAs. BIM-065 reduced ACTH, GH, chromogranin-A and PRL secretion, and increased apoptosis in corticotropinomas, somatotropinomas, and NFPAs. These effects were possibly mediated through modulation of pivotal signaling cascades like [Ca2+]i kinetic and Akt- or ERK1/2-phosphorylation. Our results unveil a robust antitumoral effect in vitro of the novel chimeric compound BIM-065 on the main PitNET subtypes, inform on the mechanisms involved, and suggest that BIM-065 could be an efficacious therapeutic option to be considered in the treatment of PitNETs.enChimeric compoundDopaminePituitary neuroendocrine tumorsReceptorSomatostatinDopamineDopamine agentsHumansNeuroendocrine tumorsPituitary neoplasmsSomatostatinTumor cells, culturedresearch article31272096Restricted AccessCélulas tumorales cultivadasDopaminaDopaminérgicosNeoplasias hipofisariasSomatostatinaTumores neuroendocrinos10.1159/0005008121423-0194https://www.karger.com/Article/Pdf/500812