(A-D) AMPK activation by metformin decreases the motility and colony formation by gastric carcinoma cells to levels comparable with Hpa2 overexpression. Cellular invasion and migration by control (Vo), Vo+metformin (0.5 mM), and Hpa2 overexpressing MKN-45 (A), BGC-823 (B), and SGC-7901 (C) cells were evaluated. Shown are representative images of invading (A) and migrating (B, C) cells taken 24 hours after cell seeding. Quantifications of the number of invading and migrating cells are shown graphically in the right panels. Colony formation by BGC-823 cells untreated or treated with metformin, and overexpressing Hpa2 is shown in (D). Quantification of colony number per dish is shown graphically at the right panel. AMPK, activated protein kinase; Hpa2, heparanase 2.