关键词: 曲格列酮, 白血病, 细胞凋亡

Abstract: AIM: To investigate the anti-prolifera-tion effect of peroxisome proliferator-activated receptor γ(PPARγ) agonist troglitazone (TGZ ) on leukemic NB4 cells and its mechanisms of action.METHODS: NB4 cells in culture medium in vitro were given differ-ent concentrations of TGZ (0-80 μmol/L) for 24, 48 and 72 h .The inhibitory rate of the cells were mea-sured by MTT assay .Cell apoptosis were observed by flow cytometry (FCM) and DNA fragmentation was as-sayed by agarose gel electrophoresis.Bcl-2 and Bax as well as Caspase-3 and poly(ADP-ribose) polymerase (PARP) expressionwere detected by Western blotting . RESULTS: TGZ (over 20 μmol/L) could inhibit the growth of NB4 cells and cause apoptosis remarkably . Furthermore, the suppression was both in time-and dose-dependent manner.DNA ladder was observed af-ter the cells treated by TGZ for 72 h, and marked mor-phological changesof cell apoptosis such as condensati-on of chromatin was clearly observed by Hoechst stain-ing .Western blotting showed cleavage of the Caspase-3 zymogen protein (32000) , with the appearance of its 20000 subunit, and a cleaved 89000 fragment of 116000 PARP was also found.Furthermore, western blotting also showed that anti-apoptotic protein Bcl-2 was decreased remarkably while pro-apoptotic protein Bax increased significantly after the cells were treated by TGZ for 48 h.CONCLUSION: TGZ can inhibit cell growth and induce apoptosis of NB4 cells via acti-vation of Caspase-3 as well as downregulation of Bcl-2 and upregulation of bax expression in NB4 cells.The results indicate that TGZ might be an important poten-tial anti-leukaemia reagent .

Key words: troglitazone, leukemia, apoptosis