Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids

Medientyp: E-Artikel

Titel: Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids

Beteiligte: Zatelli, Maria Chiara; Minoia, Mariella; Martini, Chiara; Tagliati, Federico; Ambrosio, Maria Rosaria; Schiavon, Marco; Buratto, Mattia; Calabrese, Fiorella; Gentilin, Erica; Cavallesco, Giorgio; Berdondini, Lisa; Rea, Federico; degli Uberti, Ettore C

Erschienen: Bioscientifica, 2010

Sprache: Nicht zu entscheiden

DOI: 10.1677/erc-10-0097

ISSN: 1351-0088; 1479-6821

Schlagwörter: Cancer Research ; Endocrinology ; Oncology ; Endocrinology, Diabetes and Metabolism

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Beschreibung: Bronchial carcinoids (BCs) are rare tumors originating from endocrine cells dispersed in the respiratory epithelium. It has been previously demonstrated that everolimus, or RAD001, an mTOR inhibitor, has potent antiproliferative effects in human endocrine tumors. Our aim was to evaluate the possible antiproliferative effects of everolimus in human BCs in primary culture. We collected 24 BCs that were dispersed in primary cultures, treated without or with 1 nM–1 μM everolimus, 10 nM SOM230 (pasireotide, a somatostatin receptor multiligand), and/or 50 nM IGF1. Cell viability was evaluated after 48 h, and chromogranin A (CgA) as well as vascular endothelial growth factor (VEGF) secretion was assessed after 8 h incubation. Somatostatin receptors, mTOR, and AKT expression were investigated by quantitative PCR. We found that in 15 cultures (67.5%), everolimus significantly reduced cell viability (by ∼30%; P<0.05 versus control), inhibited p70S6K activity (−30%), and blocked IGF1 proliferative effects. Everolimus also significantly reduced CgA (by ∼20%) and VEGF (by ∼15%) secretion. Cotreatment with SOM230 did not exert additive effects on cell viability and secretory activity. AKT expression was similar in responder and nonresponder tissues, while mTOR expression was significantly higher in the responder group, which was characterized by higher CgA plasma levels and bigger tumors with higher mitotic index and angiogenesis. Our data demonstrate that everolimus reduces VEGF secretion and cell viability in BCs with a mechanism likely involving IGF1 signaling, suggesting that it might represent a possible medical treatment for BCs.

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