Effects of glycogen synthase kinase inhibitor on glioblastoma multiforme cell line via apoptosis and cell signaling pathways

This failure in treatment of GBM has led researchers to investigate the molecular pathogenesis and its cellular signaling pathways. Overexpression of the epidermal growth factor receptor (EGFR) and nuclear factor kappa beta (NF-kB) play a key role in survival and proliferation of GBM. Our study was to investigate the apoptotic and molecular effects of GSK3 in GBM. Human primary glioblastoma cell line (U-87 MG) and the human fetal glial cell line (SVGp12) were used. The cells were exposed to the different doses of GSK inhibitor for 24, 48 and 72 h. Induction of apoptosis was assessed by DNA fragmentation (TUNEL) assay. EGFR and NF-kB expression was evaluated by immunofluorescence analyses. GSK3 inhibitor IX induced cytotoxicity and apoptosis in dose-dependent manner in GBM cells. Our results indicated that GSK-3 inhibitor IX induces apoptosis, resulting in a significant decrease in the expression of NF-kB and EGF. Inhibition through GSK3 has been found promising in creating therapeutic management of GBM cells. Proliferation, differentiation, cell cycle regulation, and apoptosis are mechanisms that must be interpreted as a whole. Components associated with EGFR, NF-kB, and apoptosis affect the mechanism singly and collectively. Our collective data suggest that GSK3 inhibitor IX inhibited cellular proliferation and induced apoptotic events by modulating EGFR and NF-kB expression in GBM cells. GSK3 inhibition holds promise for the development of new approaches for the therapeutic management of GBM cells.