内分泌学
内科学
垂体瘤
垂体
医学
功能(生物学)
生物
激素
细胞生物学
作者
Mari C. Vázquez‐Borrego,Antonio C. Fuentes-Fayos,Aura D. Herrera‐Martínez,Eva Venegas‐Moreno,Fernando L‐López,Alessandro Fanciulli,Paloma Moreno-Moreno,María Rosa Alhambra-Expósito,Ana Barrera-Martín,Elena de Dios,Cristóbal Blanco-Acevedo,Juan Solivera,Riccarda Granata,Rhonda D. Kineman,Manuel D. Gahete,Alfonso Soto‐Moreno,María Ángeles Gálvez-Moreno,Justo P. Castaño,Raúl M. Luque
出处
期刊:Neuroendocrinology
[S. Karger AG]
日期:2020-01-01
卷期号:110 (11-12): 1028-1041
被引量:13
摘要
Pituitary neuroendocrine tumors (PitNETs), the most abundant of all intracranial tumors, entail severe comorbidities. First-line therapy is transsphenoidal surgery, but subsequent pharmacological therapy is often required. Unfortunately, many patients are/become unresponsive to available drugs (somatostatin analogues [SSAs]/dopamine agonists), underscoring the need for new therapies. Statins are well-known drugs commonly prescribed to treat hyperlipidemia/cardiovascular diseases, but can convey additional beneficial effects, including antitumor actions. The direct effects of statins on normal human pituitary or PitNETs are poorly known. Thus, we aimed to explore the direct effects of statins, especially simvastatin, on key functional parameters in normal and tumoral pituitary cells, and to evaluate the combined effects of simvastatin with metformin (MF) or SSAs.Effects of statins in cell proliferation/viability, hormone secretion, and signaling pathways were evaluated in normal pituitary cells from a primate model (Papio anubis), tumor cells from corticotropinomas, somatotropinomas, nonfunctioning pituitary tumors, and PitNET cell-lines (AtT20/GH3-cells).All statins decreased AtT20-cell proliferation, simvastatin showing stronger effects. Indeed, simvastatin reduced cell viability and/or hormone secretion in all PitNETs subtypes and cell-lines, and ACTH/GH/PRL/FSH/LH secretion (but not expression), in primate cell cultures, by modulating MAPK/PI3K/mTOR pathways and expression of key receptors (GH-releasing hormone-receptor/ghrelin-R/Kiss1-R) regulating pituitary function. Addition of MF or SSAs did not enhance simvastatin antitumor effects.Our data reveal direct antitumor effects of simvastatin on PitNET-cells, paving the way to explore these compounds as a possible tool to treat PitNETs.