Objective     To investigate the reversal and the possible mechanism of multidrug-resistance(MDR) by dimethyl amiloride(DMA)

a specific inhibitor of Na

+

/H

+

exchanger-1(NHE-1)，in HL-60/ADM cell line in vitro.      Methods     After DMA treatment

  the chemosensitivity of HL-60/ADM cells was studi

ed by MTT assay. Intracellular concentration of daunorubicin (DNR) was determined by flow cytometry. Expression of mrp mRNA

bcl-2 mRNA

bax mRNA was assayed by semi-quantitive RT-PCR. MRP  protein expression was detected immunohistochemically. Cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).      Results     After treated with 50 μmol/L DMA for 24 h

IC

50

of HL-60/ADM cells to ADM

MIT

VCR and HAR decreased from (839.5±45.2)，(321.2±28.9)，(70.5±15.5) ，(65.2±20.7) ng/ml to (180.5±38.9)，(76.4±12.0)，(30.2±7.5)，(31.7±7.2) ng/ml. After treated with 50 μmol/L or 100 μmol/L DMA for 24 h

the intracellular concentration of DNR in HL-60/ADM cells increased from 33.56 to 48.74 or 70.10

and expression of mrp mRNA

MRP protein and bcl-2 mRNA decreased significantly

but bax mRNA increased significantly. After treated with 100 μmol/L DMA for 24 h

the rate of apoptotic cells in HL-60/ADM cells treated with 5 μg/ml ADM increased significantly.      Conclusion     DMA could reverse MDR of HL-60/ADM cells in vitro

and the mechanisms were associated with decrease of MRP expression and induction of cell apoptosis through bcl-2/bax pathway.