Abstract
Differential expression of a permeability glycoprotein (P-gp) in human myeloleukaemia K562 cells grown in the presence of the anti-cancer drug, doxorubicin, gave rise to subclones with varying degrees of resistance to other anti-tumour drugs such as vinblastine and daunorubicin. Subclones K562/MMB, MMG and MMF were produced from the parental (K562/P) cell line via limiting dilution and their MDR nature confirmed with flow cytometry using an MRK 16 monoclonal antibody directed at a surface epitope of the P-gp pump. The pattern of increasing P-gp expression in the series K562/P, MMF, MMG and MMB was paralleled by increasing resistance to vinblastine and daunorubicin. When the subclones were pre-incubated with the chemosensitizing drugs clofazimine and B669, a pattern of increasing reversal of resistance to vinblastine and daunorubicin was seen in the series K562/P, MMF, MMG and MMB.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents, Phytogenic / pharmacokinetics
-
Clofazimine / analogs & derivatives*
-
Clofazimine / pharmacology*
-
Drug Interactions
-
Drug Resistance, Multiple
-
Drug Screening Assays, Antitumor
-
Ethacrynic Acid / pharmacology
-
Flow Cytometry
-
Genistein
-
Humans
-
Isoflavones / pharmacology
-
Leukemia, Erythroblastic, Acute / drug therapy*
-
Leukemia, Erythroblastic, Acute / metabolism*
-
Tritium
-
Tumor Cells, Cultured / drug effects
-
Vinblastine / pharmacokinetics
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Antineoplastic Agents
-
Antineoplastic Agents, Phytogenic
-
Isoflavones
-
Tritium
-
Vinblastine
-
B 669
-
Clofazimine
-
Genistein
-
Ethacrynic Acid