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

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. Copyright (c) 2007 S. Karger AG, Basel.