Abstract
Resistance of tumor cells to doxorubicin is a multifactorial phenomenon. In the present investigation, the ability of resistance modifiers against different resistance mechanisms was analysed. Substances which block P-glycoprotein (P-170) function circumvented resistance of doxorubicin-resistant sarcoma 180 (S180) cells completely (verapamil, thioridazine) or partially (hycanthone), whereas inhibitors of glutathione S-transferase (ethacrynic acid, N-ethylmaleimide, buthionine sulfoximine), and protein kinase C (staurosporine, acridine orange) caused only a partial reversion of resistance. In contrast, an inhibitor of alkaline phosphatase (levamisole) did not overcome doxorubicin-resistance. These results indicate that P-glycoprotein blockers might be more effective to modulate doxorubicin-resistance of S180 cells as compared to other modifiers. Further investigations using other MDR cell lines are required to clarify the generality of these findings.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Alkaline Phosphatase / antagonists & inhibitors
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Alkaline Phosphatase / physiology
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Animals
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / physiology
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Catalase / physiology
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Cell Division / drug effects
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DNA Topoisomerases, Type II / physiology
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Dose-Response Relationship, Drug
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Doxorubicin / pharmacology*
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Doxorubicin / therapeutic use
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Drug Resistance / physiology
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Glutathione Transferase / antagonists & inhibitors
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Glutathione Transferase / physiology
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Immunohistochemistry
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / physiology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / physiology
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Radioimmunoassay
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Sarcoma 180 / chemistry
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Sarcoma 180 / drug therapy*
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Sarcoma 180 / pathology
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Topoisomerase II Inhibitors
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Tumor Cells, Cultured
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Carrier Proteins
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Membrane Glycoproteins
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Topoisomerase II Inhibitors
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Doxorubicin
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Catalase
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Glutathione Transferase
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Protein Kinase C
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Alkaline Phosphatase
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DNA Topoisomerases, Type II