Taken together, CH12 was combined with rapamycin, leading to a synergistic tumor-suppression effect on EGFRvIII+PTEN− glioblastoma in vivo via attenuating EGFR and the PI3K/AKT/mTOR pathway more effectively and reversing STAT5 activation caused by rapamycin treatment. Here, STAT5B is linked to glioblastoma.