We examined the anti-tumor efficacy of high-dose progesterone in an orthotopic GBM mouse model and evaluated the effect of progesterone on the metabolic regulators mTOR, FoxO1, Glut1, GAPDH (a glycolytic enzyme), ATP levels as an outcome of metabolic changes, and PI3K/Akt/mTOR signaling as possible mechanisms/pathways of progesterone action in GBM cells. This evidence concerns the gene HK1 and glioblastoma.