TP53 and neoplasm: Consistent with the above immunoblotting results, global gene expression profiling of U87 tumor spheres treated with vehicle, metformin, Akti-1/2, or metformin + Akti-1/2 combo identified the PI3K-AKT signaling pathway being the most affected pathway in metformin + Akti-1/2 combo-treated sphere cells, followed by p53 signaling pathway and cell cycle pathway (Fig. 3B).