Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms.
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.
Efferth
T
T
German Cancer Research Center, Heidelberg.
Volm
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002374:Catalase / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000502:physiology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000502:physiology; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011863:Radioimmunoassay; D012510:Sarcoma 180 / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin; D002374:Catalase; D005982:Glutathione Transferase; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D004250:DNA Topoisomerases, Type II