[Reversal of multidrug resistance of leukemia cell line in vitro by antisense phosphorothioate oligonucleotide]

To investigate the effectiveness of 14 mer antisense phosphorothioate oligonucleotide (AS-SODN) complementary to the published multidrug resistance gene (mdr(1) gene) sequence to reverse multidrug resistance of leukemia cell line.

50% inhibitory concentration (IC(50)) of K562 cell line resistant to adriamycin (K562/ADM cell line) was determined by the tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, the concentration of daunorubicin (DNR) in the cell by flow cytometry, the level of P170 by immunohistochemical staining technique and the level of mdr(1)-mRNA by half-quantitative RT-PCR (the ratio of mdr(1)/beta(2)-MG).

Treatment of K562/ADM cell line with 2 micromol/L AS-SODN reduced the level of both the mdr(1)-mRNA and P170. The ratio of mdr(1)/beta(2)-MG reduced from (2.07 +/- 0.16) to (1.57 +/- 0.14), and positive rate of P170 expression decreased from (98.26 +/- 1.35)% to (18.30 +/- 6.50)%. Accordingly, the concentration of DNR in cell increased. With these findings, IC(50) to ADM reduced from 25.72 mg/L to 6.97 mg/L and relative efficiency of modulation was 73.01%.

Antisense oligonucleotide targeting mdr(1) gene can reduce md(1)-mRNA, block P170 expression so as to increase the sensitivity of K562/ADM cell line to chemotherapy drugs.