Targeting the AKT Pathway in Glioblastoma Multiforme
Not peer reviewed
MetadataShow full item record
In this study, the therapeutic efficacy of AKT allosteric and ATP competitive inhibitors was investigated in EGFR-amplified SKMG-3 and EGFR-low U-87 cell lines. The IC50 values of AKT inhibitors were determined by cellular viability assay indicating that SKMG-3 cell line was more susceptible to AKT inhibition. These results were further validated by clonogenic assay. In clonogenic assay, both drugs completely inhibited colony forming ability of SKMG-3 cells at 7 μM dose while the effects were relatively less pronounced in U-87 cell line. Western blotting analyses demonstrated that both drugs inhibited AKT activity in both GBM subtypes as determined by dephosphorylation of PRAS40, a downstream target of AKT. Furthermore, both drugs induced rapid apoptosis in SKMG-3 cell line but failed to induce apoptosis in U-87 cell line upon AKT inhibition. In essence, EGFR-amplified SKMG-3 cells are more sensitive to AKT inhibitors than EGFR-low U-87 GBM subtype.
PublisherThe University of Bergen
Copyright the Author. All rights reserved