Fig. 4

PDE10A inhibition in ovarian cancer induces cyclic nucleotide signaling. A-B Pf-2545920 increases cyclic nucleotide levels in a dose-dependent manner in TOV-112D (A) and OV-90 cells (B) (cAMP 1 h treatment, cGMP 1 h 30 min treatment). Error bars, SD, **p < 0.01, ****p < 0.0001 (Ordinary one-way ANOVA). C MCI-030 treatment for 30 min increases cAMP levels in SKOV3 parental and EV 1B9 cells, but not in PDE10A KO clones. cAMP levels were measured after cell treatment with 1.5 µM MCI-030 for 30 min. Error bars, SD; *p < 0.05, **p < 0.01 (unpaired Student’s t-test). D-E MCI-030 treatment for 30 min increases cAMP levels in a dose-dependent manner in SKOV3 (D) and OV-90 (E). Error bars, SD, **p < 0.01, ***p < 0.001 (Ordinary one-way ANOVA). F Treatment with PDE10A inhibitors for 1 h induces VASP phosphorylation at serine 157 (PKA site) and serine 239 (PKG site) in a dose-dependent manner in OV-90 and (G) SKOV3 cells. GAPDH was used as a loading control