MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation.

ABSTRACT: Conventional high-grade osteosarcoma is the most common primary bone cancer with relatively high incidence in young people. Recurrent and metastatic tumors are difficult to treat. We performed a kinase inhibitor screen in two osteosarcoma cell lines, which identified MEK1/2 inhibitors. These inhibitors were further validated in a panel of six osteosarcoma cell lines. Western blot analysis was performed to assess ERK activity and efficacy of MEK inhibition. A 3D culture system was used to validate results from 2D monolayer cultures. Gene expression analysis was performed to identify differentially expressed gene signatures in sensitive and resistant cell lines. Activation of the AKT signaling network was explored using Western blot and pharmacological inhibition. In the screen, Trametinib,

SUBMITTER: Baranski Z 

PROVIDER: S-EPMC4701229 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature