Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 26 P486

ECE2011 Poster Presentations Thyroid cancer (43 abstracts)

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

C Filieri 1 , M C Zatelli 1 , M Minoia 1 , F Tagliati 1 , M Buratto 1 , M R Ambrosio 1 , M Pelizzo 2 & E C degli Uberti 1


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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