Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2016) 41 EP729 | DOI: 10.1530/endoabs.41.EP729

ECE2016 Eposter Presentations Neuroendocrinology (43 abstracts)

The cyclin-dependent kinase 4/6 inhibitor LEE001 (ribuciclib) demonstrates antiproliferative effects in neuroendocrine tumor cells in vitro

Elke Tatjana Aristizabal Prada , Svenja Nölting , Gerald Spöttl , Julian Maurer & Christoph Auernhammer


Klinikum der Universität München GEP-NET Center AG Auernhammer, Munich, Bavaria, Germany.


Cyclin-dependent kinases (CDKs) are crucial for the cell cycle regulation and alterations of the cell cycle and its regulators are often observed in human malignancies. CDK4/6 in particular orchestrates the G1 phase progression and the G1/S transition. Here we investigated the in vitro effects of the CDK4/6 inhibitor LEE001(Novartis, Basel) on the human neuroendocrine tumor (NET) cell lines BON1, QGP1 and NCI-H727. The cells were treated with different concentrations of LEE001 alone (1 nM to 10 μM) and in combination with 5-fluoruracil (5 μM) and everolimus RAD001 (10 nM). The cell viability decreased in a time- and dose-dependent manner. The combinational treatment with everolimus (RAD001) showed a significant enhancement in inhibition of cell viability when compared to single treatments in BON1, QGP1 and H727 cells. In contrast, the combinational treatment with 5-fluoruracil showed significant enhancement over single substance treatment only in H727. LEE001 showed a time- and dose-dependent G1 cell cycle arrest in all three cell lines. Western blot analysis showed that the expression level of cell cycle relevant proteins such as Checkpoint kinase 1 (Chk1), phospho-retinoblastoma (pRb) and CyclinB1/D1/D3 were altered by LEE001 treatment. Also, a compensatory upregulation of CDK4 in response to LEE001 treatment was observed. Furthermore, LEE001 treatment led to a suppression of the PI3K-Akt-mTOR pathway, as revealed by a decrease in phosphorylation of Akt and the mTOR target 4E binding protein 1. In summary, the CDK 4/6 inhibitor LEE001 exhibits promising anti-cancer properties in human NET cell lines in vitro and should be further investigated in neuroendocrine tumors.

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