Figure 3.
The combination of erlotinib and MLN0128 significantly inhibits GBM growth in vivo, in an orthotopic murine model of glioma. (a) Kaplan–Meier survival analysis of mice bearing intracranial GBM192 derived gliomas and treated with either drug alone or the combination of erlotinib and MLN0128. The treatment schedule is detailed in the methods section. * p = 0.02; **** p < 0.0001 (log-rank Mantel–Cox test). (b) Representative photomicrographs of immunohistochemical detection of EGFR (upper panels) and Ki-67 (middle panels) in GBM192 PDX samples from mice treated as indicated. Lower panels represent H&E staining for the same groups. Bar = 150 μm. (c) Quantification of EGFR intensity levels in the four different groups. Four low-magnification fields/sections were counted. We used three sections/mouse and three mice/group. (d) Ki-67 quantification was performed as described for EGFR, counting positive nuclei and calculating % positive from total nuclei. ** One-way ANOVA p < 0.05 (combination vs. vehicle).