Development of vincristine resistance and increased sensitivity to cyclosporin A and verapamil in the human U-937 lymphoma cell line without overexpression of the 170-kDa P-glycoprotein.
A vincristine (Vcr)-resistant subline of the human histiocytic lymphoma cell line U-937 (U-937-vcr) has been established and characterized with respect to its phenotypic features, including growth rate, surface marker expression and ability to respond to differentiation-inducing agents. The sensitivity of U-937-vcr cells to the direct cytotoxicity of cyclosporin A (CsA) and verapamil (Ver), and the capacity of these drugs to modify Vcr resistance, were also examined. The U-937-vcr cells exhibited a more than 200-fold resistance to Vcr, and cross-resistance to vinorelbin and taxol. Also, there was a slight cross-resistance to colchicine, doxorubicin and VP16. However, the response of U-937-vcr to CsA or Ver alone was substantially altered, with a marked decrease in their respective IC50s. The U-937-vcr cells did not show increased levels of pgp 170. We conclude that the development of Vcr resistance was not associated with a change in the major phenotypic properties of the U-937 cell line, and that resistance modifier hypersensitivity was not associated with increase in pgp 170 expression.
Botling
J
J
Department of Pathology, University Hospital, Uppsala University, Sweden.
Liminga
G
G
Larsson
R
R
Nygren
P
P
Nilsson
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000954:Antigens, Surface / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000954:Antigens, Surface; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine; D016572:Cyclosporine; D014700:Verapamil