MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro.

ABSTRACT:

Objective

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST). Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all-trans retinoic acid (ATRA). We analyzed effects of ATRA and MEK inhibitor (MEKi) combination therapy.

Methods

MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901. We assessed cell viability, proliferation, migration, apoptosis and differentiation as well as mRNA expression of RAR and RXR subtypes and ATRA target genes such as CRABP2, CYP26A1, RARB and PDK1. We also analyzed CRABP2 methylation in cell lines and performed immunohi

SUBMITTER: Fischer-Huchzermeyer S 

PROVIDER: S-EPMC5683628 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature