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.
Vasanthakumar
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Molecular Biology Section, Southern Research Institute, Birmingham, AL 35255-5305.
Ahmed
N K
NK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003630:Daunorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides / Q000378:metabolism / Q000494:pharmacology*; D063065:Organophosphonates / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D063065:Organophosphonates; D003630:Daunorubicin