Synergistic effect of perampanel with temozolomide on glioblastoma cells in vivo

The anti-epileptic drug perampanel, an α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist, exhibits anti-tumor effects against glioblastoma cells in vitro. This study examined the anti-tumor effects of combination therapy with temozolomide and perampanel on glioblastoma cells both in vitro and in vivo to assess the potential for clinical application. The commercially available glioblastoma cell line U-87MG and the newly established glioblastoma cell line 0125-DGC were used. The anti-tumor effect of perampanel and combination therapy with temozolomide was evaluated as growth inhibition of glioblastoma cells by counting the numbers of cells. Furthermore, a brain tumor mouse model was created by transplanting U-87MG cells into the brains of immunodeficient mice. Brain tumor mouse models were divided into 4 groups: control group, temozolomide administration group, perampanel administration group, and temozolomide-perampanel combined administration group, and the survival times were compared. The number of viable cells decreased significantly after 1 μM administration of perampanel in vitro in both cell lines. The half-maximal inhibitory concentration values of perampanel were 78.4 μM for U-87MG and 81.8 μM for 0125-DGC. In addition, the combination of 10 μM perampanel and temozolomide significantly inhibited cell proliferation compared to only perampanel or temozolomide in both cell lines. In the animal experiments, mice treated by the combination therapy of temozolomide and perampanel demonstrated significantly longer survival times (median survival time 52.0 days) than the control group (30.0 days), perampanel administration group (34.0 days), and temozolomide administration group (41.0 days). This study demonstrated that the combination of temozolomide and perampanel demonstrates a stronger anti-tumor effect than either single drug in vitro, and significantly prolonged survival time in vivo.