Modulation of drug resistance in a daunorubicin resistant subline with oligonucleoside methylphosphonates.

Human K562 erythroleukemia cells were selected in sequential steps for resistance to daunorubicin (K562/III) and found to be cross-resistant to a number of drugs, including vincristine, dactinomycin, doxorubicin, etoposide, and teniposide. In this paper, we report that the K562/III subline showed amplification of an mdr1 gene and its 4.5 kb transcript. Our results also show that non-ionic oligonucleoside methylphosphonates, complementary to the initiation codon and 15 bases upstream of the mdr1 gene, can completely inhibit the synthesis of P-glycoprotein and partially increase the toxicity of daunorubicin.