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Endocrine Abstracts (2017) 49 EP196 | DOI: 10.1530/endoabs.49.EP196

1Section of Endocrinology, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy; 2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; 3Laboratorio in Rete del Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of Ferrara, 44121 Ferrara, Italy.

: Pancreatic neuroendocrine tumours (pNETs) are rare neoplasms arising from the endocrine pancreas. The fist line treatment is surgery that is often not curative in the presence of metastatic disease. Therefore, there is an increasing need for medical therapy. Sunitinib is a multi-target receptor tyrosine-kinase (RTK) inhibitor, described as having as main target VEGF receptor, with antitumor and antiangiogenic effects, approved for pNETs medical treatment. This study is aimed at evaluating Sunitinib effects in the human pNET cell line, BON1, in order to identify tissue-specific molecular targets that might predict the efficacy of the treatment. We tested BON1 cell viability and proliferation by means of Proliferation Assay and Luminescent Cell Viability Assay after treatment with Sunitinib (0.25–7.5 μM) and found an IC50=5 μM. Western blot analysis confirmed that BON1 cells express VEGF, IGF1 and EGF receptors, therefore we tested the effects of VEGF 50 ng/ml, IGF1 100 nM and EGF 15 nM alone or each in combination with Sunitinib 5 μM. We found that BON1 cell viability is not affected by VEGF and EGF, while it is significantly enhanced by IGF1 (+20%; P<0.05), that was capable of blocking the antiproliferative action of Sunitinib, suggesting that the main target of this drug is IGF1 receptor. Therefore, we tested Linsitinib, a specific IGF1 receptor inhibitor, and found that it significantly reduces BON1 cell viability (−25%; P<0.05) and blocks the proliferative effects of IGF-1. These data indicate that IGF1 receptor represents the main molecular target of Sunitinib in BON1 cells and that it may play a crucial role in pNET cell proliferation control, suggesting that Linsitinib might be an effective medical treatment.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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