The inhibitory effect of a novel phosphodiesterase 4 inhibitor ZL-n-91 on proliferation of osteosarcoma U20S cells / 中国药理学通报

Aim To explore the anti-cancer effects of ZL-n-91, a novel and highly selective phosphodiesterase 4 inhibitor, on the osteosarcoma U2OS cells.Methods CCK-8 assay was used to detect the inhibitory effect of ZL-n-91 with different concentrations(0, 20, 40, 80, 160, 240, 320, 400, 480 μmol·L-1)and different intervention time(0, 24, 48, 72, 96 h)on the proliferation of U2OS cells.Tablet clone forming experiment was used to detect the effect of ZL-n-91 on the clonality of U2OS cells.Flow cytometry was used to detect the cell apoptosis and cell cycle distribution.Western blot was employed to detect the expression of Bcl-2, CDK2, CDK4, CyclinD1, CyclinE1 protein.Results The inhibitory rate of ZL-n-91 on U2OS cells was concentration- and time-dependent(P<0.05), and its half inhibition rate IC50 was 174.1 μmol·L-1.ZL-n-91 significantly inhibited the clonality of U2OS cells(P<0.01).ZL-n-91 significantly induced cell apoptosis, and caused cell cycle arrest at G0/G1 phase in U2OS cells(P<0.01).The results of Western blot showed that ZL-n-91 significantly down-regulated the expression of Bcl-2, CDK2, CDK4, CyclinD1, CyclinE1 proteins in U2OS cells(P<0.05).Conclusions The novel selective phosphodiesterase 4 inhibitor, ZL-n-91, can significantly inhibit the proliferation of osteosarcoma U2OS cells with induction of cell cycle arrest and cell apoptosis, and may become a potential anti-cancer agent.