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.
mTOR inhibition hampers cell viability in selected human medullary thyroid carcinoma primary cultures
FILIERI, Carlo;ZATELLI, Maria Chiara;MINOIA, Mariella;TAGLIATI, Federico;BURATTO, Mattia;AMBROSIO, Maria Rosaria;DEGLI UBERTI, Ettore
2011
Abstract
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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
