Endocrine Abstracts (2011) 26 P486

mTOR inhibition hampers cell viability in selected human medullary thyroid carcinoma primary cultures

C Filieri1, M C Zatelli1, M Minoia1, F Tagliati1, M Buratto1, M R Ambrosio1, M Pelizzo2 & E C degli Uberti1

1Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy; 2Department of Medical and Surgical Science, General Surgery III, University of Padova, Padova, Italy.

It has been demonstrated that everolimus, an mTOR inhibitor, has potent anti-proliferative effect in a human Medullary Thyroid Carcinoma (MTC) cell line, TT, and in two human MTC primary cultures. We aimed at evaluating the possible antiproliferative effects of everolimus in a group of 20 human MTC in primary culture. To this purpose, 20 MTCs were dispersed in primary cultures, treated without or with 1 nM – 1 μM everolimus, 10 nM SOM230, and/or 50 nM IGF1. Cell viability and apoptosis were evaluated after 48 h and Calcitonin (CT) secretion was assessed after a 8 h incubation. Somatostatin receptor expression was investigated by quantitative PCR. We found that in 14 cultures everolimus reduced cell viability (~40%), promoted apoptosis (+30%), inhibited p70S6K activity (−20%) and blocked IGF1 proliferative and anti-apoptotic effects. In selected tissues co-treatment with SOM230 had additive effects. It did not affect CT secretion, but blocked the stimulatory effects of IGF1. In conclusion, everolimus reduced MTCs cell viability by inducing apoptosis, with a mechanism likely involving IGF1 signalling but not CT secretion, suggesting that it might represent a possible medical treatment for persistent/recurrent MTCs.

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