High doses of cGMP-PDE inhibitors suppress growth of LS174T colon cancer cells by a cGMP-independent mechanism. Parental and PKG2-expressing LS174T colon cancer cells were treated for 3 days with different doses of PDE inhibitors. Sildenafil (Sil)-PDE5, PF-04447943 (PF)-PDE9, and TAK-063 (TAK)-PDE10a. The effect of PDE inhibitor treatment on (A) cell proliferation (hemocytometer), and (B) cell viability (trypan blue exclusion). (C) The effect of PDE inhibitors on cGMP levels in LS-174T-PKG2 cells was measured by immunoblotting for phosphorylation of VASP (VASP-239P). Data show means, and error bars are S.D. ***P < 0.0001, **P < 0.005, *P < 0.05.