The Effect of Novel Phosphodiesterase 4 Inhibitor ZL-n-91 to the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562.@*METHODS@#CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC@*RESULTS@#ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05).@*CONCLUSION@#The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.

Anxiolytic-like effect of etazolate, a type 4 phosphodiesterase inhibitor in experimental models of anxiety.

Etazolate is a selective inhibitor of type 4 phosphodiesterase (PDE4) class enzyme. Antidepressant-like effect of etazolate has been previously demonstrated in the rodent models of depression. The present study was designed to investigate the anxiolytic-like activity of etazolate in experimental mouse models of anxiety. The putative anxiolytic effect of etazolate (0.25-1 mg/kg, ip) was studied in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark (L/D) aversion, hole board (HB) and open field (OFT) with diazepam (2 mg/kg, ip) as reference anxiolytic. Like diazepam (2 mg/kg, ip), etazolate (0.5 and 1 mg/kg, ip) significantly increased the percentage of both time spent and entries into open arms in the EPM test. In the L/D test etazolate (0.5 and 1 mg/kg, ip) increased the both total time spent in and latency time to leave the light compartment. Etazolate (0.5 and 1 mg/kg, ip) also significantly increased head dipping scores and time spent in head dipping, whereas significantly decreased the head dipping latency in HB test. In addition, etazolate (0.5 and 1 mg/kg, ip) significantly increased the ambulation scores (square crossed) and number of rearing in OFT. In conclusion, these findings indicated that etazolate exhibited an anxiolytic-like effect in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.