Fig. 1

V-4084 inhibits HGF-autocrine GBM proliferation and invasion. a By day 3, U87M2 cells had dispersed significantly (top panel). While V-4084 and its derivative V-837980 significantly inhibited U87MG dispersal at 1 μM, TMZ at 50 μM failed to show any activity. b U87M2 cells constitutively show P-MET, P-MAPK, and activate AKT following HGF. V-4084 inhibited HGF-dependent downstream pathways (MET and MAPK) in U87MG dose-dependently. c To evaluate V4084 efficacy orthotopically, U87M2 cells expressing a luciferase reporter gene (U87M2Luc+) were inoculated into nude mice orthotopically, and tumor growth was monitored by BLI twice a week. V4084 at 30 mg/kg significantly inhibited tumor growth orthotopically (1 week of dosing, one dose per day; p < 0.05). DBM2 showed no response to V-4084. d V-4084 dose-dependently inhibited HGF-autocrine (U87M2, U118, and SF295) subcutaneous tumor growth, but had no effect against tumors without HGF expression (U251M2 and DBM2)