OBJECTIVE: To study the mechanism of inhibitory effect of
Ubenimex on human leukemic cells. METHODS: K562 and HL60 cells were treated with
Ubenimex at different concentrations, and the growth inhibition was analysed by MTT assay. Cell apoptosis was evaluated by light microscopy, agrose gel electrophoresis, TUNEL labeling method and flow cytometry (FCM) assay. RESULTS: (1)Treatment with
Ubenimex remarkably inhibited the growth of HL60 cells, the IC(50) of
Ubenimex for HL60 cells was 13.03&mgr;g/ml. But K562 cells were less sensitive than HL60.
Ubenimex inhibited the growth of HL60 and K562 cells in a dose-dependent manner. (2)Apoptosis of leukemic cells was induced by
Ubenimex, which was shown by the changes in morphology,
DNA ladder on agrose gel, TUNEL labeling,typical peak before G1 phase of cell cycle and the positive of
Annexin V(FITC) on the cells membrane with FCM. (3)
Ubenimex induced apoptosis of K562 and HL60 cells in a dose-and-time-dependent manner. (4)The cell cycle analysis by FCM showed that the HL60 cells were blocked in G1 phase after treated by
Ubenimex. Conclution
Ubenimex can efficiently induce apoptosis of HL60 and K562 cells, this may be one of the mechanisms for inhibiting effect of
Ubenimex on
leukemia.