Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P801

ICEECE2012 Poster Presentations Endocrine tumours and neoplasia (112 abstracts)

mTOR inhibitors hamper cell viability in selected human medullary thyroid carcinoma primary cultures

M. Minoia , M. Rossi , E. Gentilin , D. Molè , E. degli Uberti & M. Zatelli


University of Ferrara, Ferrrara, Italy.


Introduction: It has been demonstrated that mTOR inhibitors have potent anti-proliferative effects in a human Medullary Thyroid Carcinoma (MTC) cell lines. We here explore the possible role of mTOR inhibitors, Everolimus and BEZ235 (which also inhibits the PI3K pathway) on the effects of Insulin-like Growth Factor-1 (IGF-1) in human MTC primary cultures.

Aims: To this purpose, 20 MTCs primary cultures, were treated without or with 1 uM Everolimus, 10 nM BEZ235, and/or 50 nM IGF-1.

Materials and methods: Cell viability and apoptosis were evaluated after 48 h. p70S6K phosphorylation was evaluated by ELISA.

Results: we observed that Everolimus and BEZ235 significantly reduced MTC cell viability, by 20 and 35% respectively, while IGF-1 enhanced cell viability, an effect completely blocked by mTOR inhibitors. Co-incubation with an IGF-1R blocking antibody enhanced the antiproliferative effects of. Everolimus and BEZ235. Caspase activity was enhanced by BEZ235 and reduced by IGF-1, an effect that was attenuated by co-treatment with mTOR inhibitors. Phosphorylation of p70S6K, a down-stream mTOR effector in the PI3K/Akt pathway, was evaluated to assess whether this effect is due to variations in mTOR activity. We observed that IGF-1 enhanced p70S6K phosphorylation, that is reduced by mTOR inhibitors, indicating that IGF-1 exerts its proliferative effects by inducing this pathway.

Conclusion: In conclusion, mTOR inhibitors reduced MTCs cell viability by inducing apoptosis, with a mechanism likely involving IGF-1 signalling, suggesting that these drugs might represent a possible medical treatment for persistent/recurrent MTCs.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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