PDE4B expression modulates the activity of the SYK inhibitor Piceatannol. (A) Dose-response curves and cellular IC₅₀ of Piceatannol for DLBCL cell lines genetically modified to express high or low levels of PDE4B. (Top panel) Constitutive expression of PDE4B-WT in DHL6 and DHL10 significantly impaired the growth inhibitory efficacy of the SYK inhibitor Piceatannol. IC_50s of 12.5 ± 0.7 μM versus 4.32 ± 0.7 μM and 31.7 ± 1.5 μM versus 19.3 ± 1.0 μM were found for DHL6 and DHL10, expressing PDE4B-WT and PI mutant, respectively (P < .01, log IC₅₀ comparisons). (Bottom panel) Likewise, stable expression of 2 distinct PDE4B shRNA constructs in the DLBCL cell line OCI-Ly3, significantly improved Piceatannol efficacy; sh-PDE4B no. 2 (IC₅₀, 12.3 ± 1.5 μM vs 23.1 ± 1.2 μM, sh-control cells) and sh-PDE4B no. 5 (IC₅₀, 10.1 ± 2.7 μM vs 22.6 ± 1.9 μM, sh-control cells; P < .01, log IC₅₀ comparisons). In the x axis, the log values of the Piceatannol concentration are shown in a linear scale. All growth inhibition curves were generated in triplicate. (B) Apoptosis rate in OCI-Ly3 cells stably expressing a shRNA-control or sh-RNA directed to PDE4B. Knockdown of PDE4B expression significantly enhances the 10 μM Piceatannol-induced apoptosis in DLBCL (P < .05, one-way ANOVA). Data shown is the mean + SE of 2 independent experiments for each unique PDE4B shRNA sequence.