DRD2 agonist cabergoline abolished the escape mechanism induced by mTOR inhibitor everolimus in pituitary neuroendocrine tumoral cells

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Introduction: The mTOR inhibitor everolimus displays antimitotic effects on diverse neoplasms, including pituitary neuroendocrine ones (PitNETs); however, its effect is reduced by an escape mechanism that increases AKT phosphorylation (p-AKT) leading to survival pathway activation. Dopamine receptor type 2 (DRD2) reduces p-AKT in some non-functioning PitNETs (NF-PitNETs) and in lactotrophs MMQ cells, through a β-arrestin2-dependent mechanism.

Aim(s): This study aims to analyse the efficacy of everolimus combined with DRD2 agonist cabergoline in reducing proliferation in primary cultured NF-PitNETs and MMQ cells, to analyse AKT and β-arrestin2 activity.

Materials and methods: Cells proliferation was tested trough BrdU-incorporation assays, protein levels by western blot analysis. Silencing was performed with β-arrestin2 siRNAs.

Conference:

Presenting Author:

Authors: Mangili F, Esposito E, Treppiedi D, Catalano R, Marra G,

Keywords: pituitary neuroendocrine tumor, everolimus, mTOR/AKT pathway, β-arrestin 2, dopamine receptor type 2, cabergoline,