(A) Simvastatin dose-dependently decreased RhoA activity in U251MG and G34. (B), (C), (D), SMAD3 knockdown reduced SBE4 luciferase activity and cell proliferation and ameliorated simvastatin's effects on TGF-β reporter activity and cell proliferation in U251MG (B), in GICs JWL-022, JWL-131 and G34 (C), and in multiple other cancer types (D). (E) Simvastatin reduced Smad3 phosphorylation at ser208 in U251MG (top panel) and basal and exogenous TGF-β-induced Smad3 phosphorylation at ser208 in G34 (bottom panel). (F) Cell counts of adherent G34 and JWL-131 GICs after six days of simvastatin +/-exogenous TGF-β. Sim: simvastatin. All values are the mean±SD of three experiments. *, P<0.05; **, P<0.01. ***, P<0.001. ****, P<0.0001.