Mechanisms involved in the development of adriamycin resistance in human leukemic cells.
We have developed three adriamycin (ADR)-resistant K562 sublines with different degrees of resistance. These sublines show a decreased accumulation and an increased efflux of ADR in proportion to the degree of resistance. Two membrane proteins (mol. wt 170,000 and 230,000) reactive with monoclonal antibody against P-glycoprotein were highly expressed in both the K562/ADR200 and the K562/ADR500 subline. Less resistant K562/ADR80 cells contained only small amounts of mol. wt 230,000 protein. Thus, the level of P-glycoprotein expression was not proportionate to the degree of ADR efflux. Verapamil treatment could not completely reverse ADR resistance. No significant change of glutathione-s-transferase activity nor in the level of DNA topoisomerase II was detected in resistant sublines. In our sublines it seems that P-glycoprotein is one of the mechanisms for resistance, but additional mechanisms may be involved.
Kato
S
S
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ideguchi
H
H
Muta
K
K
Nishimura
J
J
Nawata
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000032:analysis; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D014700:Verapamil; D005982:Glutathione Transferase; D004264:DNA Topoisomerases, Type I