Perampanel Inhibits Neuroblastoma Cell Proliferation Through Down-regulation of AKT and ERK Pathways.

Abstract

Activation of AKT serine/ threonine kinase (AKT) predicts poor outcome in neuroblastoma, which highlights the potential of the AKT pathway as a promising target for neuroblastoma treatment. Several studies reported that blockade of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) reduces proliferation in glioblastoma or lung cancer by inhibiting AKT and extracellular signal-related kinase (ERK) pathways. In this study, we examined the effect of the AMPAR antagonist perampanel on human neuroblastoma cells. Cell proliferation, caspase activity, and western blot assays were performed to determine the effect of perampanel on the KP-N-SI9s human neuroblastoma cell line. Perampanel inhibited cell proliferation without triggering apoptosis in neuroblastoma cells. Down-regulation of AKT protein levels, AKT phosphorylation, and ERK1/2 phosphorylation were also observed in neuroblastoma cells with perampanel treatment. Perampanel inhibits neuroblastoma cell proliferation through down-regulation of AKT and ERK pathways and has potential for the treatment of neuroblastoma.