Effects of ALK inhibitory treatment with alectinib in glioblastoma cells

Anaplastic lymphoma kinase (ALK) is expressed in around 60% of glioblastomas and conveys tumorigenic function. Therefore, ALK inhibitory strategies with alectinib were investigated in glioblastoma cells. We demonstrated that alectinib inhibited proliferation and clonogenicity of ALK expressing glioblastoma initiating cells, whereas cells without ALK expression or after ALK depletion via knockdown showed primary resistance against alectinib. The aim of this analysis was to investigate molecular mechanisms of alectinib mediated treatment effects in the ALK expressing S24 cells, which represent a primary glioblastoma cell culture, and after knockdown of ALK. S24 cells were treated for 24h with 500nM alectinib or respective DMSO amounts as treatment control. Total mRNA was isolated from three replicates and were used for analysis of molecular mechanisms of alectinib mediated treatment effects. ALK knockdown was performed using commercial lentiviral small hairpin RNAs. ALK knockdown cells were treated with 500nM alectinib and respective DMSO amounts as treatment control. Total mRNA was isolated from three replicates and were used to analyze potential off-target treatment effects of alectinib.