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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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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