Chemoresistance to doxorubicin and cisplatin in a murine cell line. Analysis of P-glycoprotein, topoisomerase II activity, glutathione and related enzymes.
Resistance to antineoplastic drugs has often been associated with P-glycoprotein overexpression, this certainly being not the sole mechanism. In order to characterize resistance to doxorubicin and cisplatin, we have analysed P-glycoprotein expression, topoisomerase II activity, glutathione and related enzymes in murine leukemic cells (doxorubicin or cisplatin-resistant). The doxorubicin-resistant cells contained P-glycoprotein, showed lower activities of glutathione S-transferase well as of glutathione reductase and topoisomerase II. The modifications observed in the most cisplatin-resistant cell line were a higher activity of glutathione S-transferase isoenzyme pi and topoisomerase II. These results suggest that drug uptake, glutathione metabolism as well as topoisomerase II activity are all characteristic of multidrug resistance.
Mestdagh
N
N
Université de Lille II, Institut de Chimie Pharmaceutique, France.
Pommery
N
N
Saucier
J M
JM
Hecquet
B
B
Fournier
C
C
Slomianny
C
C
Teissier
E
E
Hénichart
J P
JP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis*; D002945:Cisplatin / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005978:Glutathione / Q000032:analysis*; D005982:Glutathione Transferase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D004317:Doxorubicin; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II; D005978:Glutathione; D002945:Cisplatin