Glioblastoma (GBM) is the most common brain tumor with high abilities of proliferation, migration and invasion. As is well-known, the peritumoral excitotoxic neuronal cell loss caused by glutamate, secreted by GBM cells, through activated N-methyl-D aspartate receptor (NMDAR) of neuronal cell. What's more, glutamate benefits the migration of GBM cells. However, the glutamate will not kill the GBM cells itself, which may be due to the deficiency of NMDAR. Fasudil, a ROCK inhibitor, was applied for subarachnoid hemorrhage (SAH) in clinic for many years. And it was found to be of potential to inhibit the proliferation, migration and invasion of GBM cells. In present study, we applied fasudil on the primary human GBM cells to further investigate the reduction of cell viability combined with glutamate. Combination treatment of glutamate and fasudil could significantly decrease the cell viability and elevate the level of LDH compared with fasudil treatment alone. What's more, MK-801, a NMDAR antagonist, could partially abolish this death caused by combination treatment. Further study found that the expression level of NMDAR-2B was elevated after treatment with fasudil in GBM cells. These results demonstrated fasudil could increase the expression level of NMDAR, which is necessary for glutamate to work. In a word, our research has provided a new sight of medicine combination in the treatment of GBM.
Keywords: Glioblastoma; NMDAR; fasudil; glutamate.