a, An illustration showing MK-8931 treatment schedule in GSC-derived xenograft models. Briefly, human glioma stem cells (GSCs) expressing luciferase (Luc) were transplanted into NSG mouse brains through intracranial injection (ICI) to establish GBM xenografts. Seven days after transplantation, the tumor-bearing mice were treated with MK-8931 (30 mg/kg/daily) or the vehicle control by oral gavage. Bioluminescent imaging (IVIS) were performed twice per week to monitor tumor growth before and after MK-8931 treatment. Mice were maintained until the development of neurological signs to examine the effect of MK-8931 treatment on survival. Mouse brains bearing GBM tumors were harvested for further analyses.
b,c, Representative bioluminescent images (b) of intracranial GBM xenografts derived from CCF-3264 or CCF-DI315 GSCs expressing luciferase in mice treated with MK-8931 (30 mg/kg/daily) or the vehicle control. Quantifications (c) show the mean bioluminescence of the MK-8931-treated or control group on the indicated days after GSC transplantation. Data are shown as means ± SEM. n = 7 GBM-bearing mice per group. Statistical significance was determined by two-tailed Student’s t-test; p values were indicated on the figure.
d, Kaplan-Meier survival curves of mice bearing GSC-derived GBM xenografts treated with MK-8931 (30 mg/kg/daily) or the vehicle control. n = 8 mice per group (CCF-3264 GSC-derived xenografts) or 7 mice per group (CCF-DI315 GSC-derived xenografts). Log-rank analysis was used to assess the significance; p values are indicated on the figure.