In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1-mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells.
To establish whether MRP1 gene copy number is a common feature of the upregulation of MRP1 expression in cancer patients, we studied the MRP1 gene copy number in leukemia patients by fluorescent in situ hybridization (FISH) and real-time PCR.
To determine the antitumor effect of arsenic trioxide (As2O3) on multidrug-resistant cells, we applied 3 human leukemia cell lines: daunorubicin (DNR)-resistant cell line K562/D1-9, which overexpresses p-glycoprotein (Pgp); DNR and 1-beta-D-arabinofuranosylcytosine (Ara-C) double-resistant cell line HL60/AD, which overexpresses multidrug resistance-associated protein (MRP1); and Bcl-2-transfected pre-B lineage leukemia cell line 697/Bcl-2.
Pgp activity was higher in CD34+ leukemia than in CD34- leukemia (2.26 +/- 1.50 vs 1.46 +/- 1.21 respectively, p = 0.003) and MRP1 activity was higher in CD34- leukemia than in CD34+ leukemia (1.77 +/- 0.40 vs 1.4 +/- 0.29 respectively, p = 0.004).
Pgp activity was higher in CD34+ leukemia than in CD34- leukemia (2.26 +/- 1.50 v 1.46 +/- 1.21, respectively; P = .003), and MRP activity was higher in CD34- leukemia than in CD34+ leukemia (1.77 +/- 0.40 v 1.4 +/- 0.29, respectively; P = .004).
Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonine-selected K562 human leukemia cell lines.