title: Chemoresistance to doxorubicin and cisplatin in a murine cell line. Analysis of P-glycoprotein, topoisomerase II activity, glutathione and related enzymes.
abstract: 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.
authors.affiliation: Université de Lille II, Institut de Chimie Pharmaceutique, France.
authors.forename: N
authors.initials: N
authors.lastname: Mestdagh
authors.forename: N
authors.initials: N
authors.lastname: Pommery
authors.forename: J M
authors.initials: JM
authors.lastname: Saucier
authors.forename: B
authors.initials: B
authors.lastname: Hecquet
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.forename: C
authors.initials: C
authors.lastname: Slomianny
authors.forename: E
authors.initials: E
authors.lastname: Teissier
authors.forename: J P
authors.initials: JP
authors.lastname: Hénichart
mesh_terms: 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
chemical_list: 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