Dual Inhibition of PI3K and mTORC1/C2 by PKI-587 (PF-05212384) as a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease and Its Effect on AKT-Signaling


Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are heterogeneous in their clinical behavior and therapeutic options are still not satisfactory. The “crosstalk” of different signaling pathways in NEN cells appears to be more complex as known already. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.

Aim(s): Therefore, we assessed the effects of PKI-587 in different GEP-NEN cell lines compared to the established mTORC1 inhibitor RAD001.

Materials and methods: We treated the cell lines BON, QGP-1, KRJ-1 and LCC-18 with increasing concentrations of the inhibitor PKI-587, compared to RAD001 and DMSO. We performed WST-1 assay to determine efficacy and growth inhibition. The induction of apoptosis was shown by caspase 3/7 activation and cell cycle was analyzed by FACS. We determined alterations of signaling mediators by phosphor-specific Western Blot analysis.

Conference: 12th Annual ENETSConcerence (2015)

Presenting Author:

Authors: Freitag H, Briest F, Christen F, Grass I, Lewens F,

Keywords: dual inhibition, PI3K, mTOR, PKI-587,RAD001, signaling,

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