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Targeting the AKT Pathway in Glioblastoma Multiforme

Latif, Md Abdul
Master thesis
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URI
https://hdl.handle.net/1956/13020
Date
2016-06-01
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  • Department of Biomedicine [453]
Abstract
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.
Publisher
The University of Bergen
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Copyright the Author. All rights reserved

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