Combined Blockade of Several Signalling Pathways Shows Marked Anti-Tumor Potential in Two Novel Mouse Phaeochromocytoma Cell Lines

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Introduction: The current study explores novel targeted therapies for malignant pheochromocytomas (PCCs) and paragangliomas, utilizing a more benign (MPC) and a more malignant (MTT) PCC cell line. We have previously shown that the dual PI3K/mTORC1 inhibitor NVP-BEZ235 significantly reduced MPC and MTT cell viability, but increased ERK signalling.

Aim(s): We have now investigated the combination of NVP-BEZ235 with the established agent lovastatin, as this has been described to inhibit ERK signalling.

Materials and methods: Both cell lines, generated from heterozygous Neurofibromin 1 knock-out-mice, were treated with varying doses of lovastatin, NVP-BEZ235, or the combination of lovastatin and NVP-BEZ235, for different time periods. Metabolic viability was assessed by cell proliferation assay (MTS). Protein levels of phospho-(p) and total AKT, ERK and p70S6K were assessed by Western blotting in MPC cells.

Conference: 9th Annual ENETSConcerence (2012)

Presenting Author:

Authors: Noelting S, Garcia E, Alusi G, Korbonits M, Grossman A,

Keywords: pheochromocytoma, cell lines, proliferation, MAPK, mTOR,