Inhibiting receptor tyrosine kinase AXL with small molecule inhibitor BMS-777607 reduces glioblastoma growth, migration, and invasion in vitro and in vivo.

ABSTRACT:

Purpose

Receptor tyrosine kinase AXL (RTK-AXL) is regarded as suitable target in glioma therapy. Here we evaluate the anti-tumoral effect of small molecule inhibitor BMS-777607 targeting RTK-AXL in a preclinical glioma model and provide evidence that RTK-AXL is expressed and phosphorylated in primary and recurrent glioblastoma multiforme (GBM).

Experimental design

We studied the impact of BMS-777607 targeting RTK-AXL in GBM models in vitro and in vivo utilizing glioma cells SF126 and U118MG. Impact on proliferation, apoptosis and angiogenesis was investigated by immunohistochemistry (IHC) and functional assays in vitro and in vivo. Tumor growth was assessed with MRI. Human GBM tissue was analyzed in terms of RTK-AXL phosphorylation by immunoprecipitation and immunohistochemi

SUBMITTER: Onken J 

PROVIDER: S-EPMC4891090 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature