HZ08 reverses multidrug resistance in leukemia cells by reducing glucosylceramide synthase and MDR1

In this paper the influence of HZ08 on multidrug resistance and possible mechanism were explored.It was found that the IC₅₀of adriamycin in the presence of 10 μmol/L HZ08 in clinical sample cells was 0.60 μmol/L,while the IC₅₀in K562/A02 cells was 0.83 μmol/L by MTT.The reversal folds of MDR were 27.87 and 20.49,respectively.For further mechanism study of HZ08,the expression level of glucosylceramide synthase (GCS) protein in K562/A02 and resistant cells from clinical samples were analyzed by Western blot,while the mRNA of MDR1 was detected by real-time fluorescent quantitative polymerase chain reaction (FQ-RT-PCR).Combined with adriamycin,all concentrations (15,20,25 μmol/L) of HZ08 decreased the expression of GCS protein.In addition,compared with the group of treatment with adriamycin alone,combined treatment of HZ08 and adriamycin decreased the expression of MDR1 significantly (P<0.01).Therefore,HZ08 possibly reverses multidrug resistance by its joint action with adriamycin on GCS and MDR1 in both cell line and clinical sample cells.