Publikation

The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Wissenschaftlicher Artikel/Review - 19.02.2007

Bereiche
PubMed
DOI

Zitation
Zitzmann K, De Toni E, Brand S, Göke B, Meinecke J, Spöttl G, Meyer H, Auernhammer C. The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 2007; 85:54-60.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Neuroendocrinology 2007; 85
Veröffentlichungsdatum
19.02.2007
ISSN (Druck)
0028-3835
Seiten
54-60
Kurzbeschreibung/Zielsetzung

BACKGROUND/AIM
Tumors exhibiting constitutively activated PI(3)K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3)K/Akt/mTOR signaling.

METHODS
BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation.

RESULTS
RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis.

CONCLUSION
In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients.