SFEBES2015 Poster Presentations Pituitary (48 abstracts)
In vitro effects of Imatinib on somatotrophinoma cell line
Prakamya Gupta 1 , Ashutosh Rai 1 , Naresh Sachdeva 1 , Bishan Das Radotra 1 , Anil Bhansali 1 , Kanchan Kumar Mukherjee 1 , Debashish Hota 1 , Márta Korbonits 2 & Pinaki Dutta 1
1Postgraduate Institute of Medical Education and Research, Chandigarh, India; 2Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University, London, UK.
Introduction: Acromegaly is a neuroendocrine disorder caused by excessive secretion of growth hormone (GH). Current treatment includes surgery, radiotherapy and drugs like somatostatin or dopamine receptor agonist. In spite of combination of therapies cure rate is dismal. There is a quest for new therapeutic targets with optimal efficacy, least side effect without any cost constraints. Recently, a few reports have shown that tyrosine kinase inhibitor (Imatinib) causes growth failure in pediatric chronic myeloid leukemia (CML) cases probably by targeting the GH/IGF-1 axis. There is no study to report the effect of TKI on pituitary adenoma either in vitro or in vivo. Here we present data on the effect of Imatinib on GH release from primary cultures of human somatotrophinoms.
Materials and methods: Primary culture was performed on tumor samples obtained from 15 acromegaly patients undergoing transsphenoidal surgery. Pure somatotrophinoma population was obtained by cell sorting using GHRHR-FITC labelled antibody. Selected cells were treated with different concentrations of Imatinib (0–10 μM). We studied cell viability (MTT assay), GH release, GH protein expression (immunocytochemistry) and cell morphology with electron microscopy. Similar experiments were performed on rat somatomammotroph GH3 cells (ATCC, USA).
Results: Low concentration (0.5 μM) of Imatinib reduced GH positivity with immunostaining and GH secretion in both human somatotroph primary culture and GH3 cells. Electron microscopy of Imatinib-treated cells exhibited a reduction in GH positive granules. GH inhibition appears at a concentration of 0.5 μM of Imatinib without any added advantage of increasing concentrations. On the other hand, Imatinib did not show any effect on cell viability.
Conclusion: Imatinib inhibits GH secretion in somatotrophinoma cells without affecting cell viability. We provide new insights into use of tyrosine kinase inhibitor- Imatinib as an alternative treatment for GH-secreting pituitary adenomas.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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