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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
Author(s) -
Botling Johan,
Liminga Gunnar,
Larsson Rolf,
Nygren Peter,
Nilsson Kenneth
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580221
Subject(s) - vincristine , verapamil , lymphoma , p glycoprotein , cell culture , cancer research , glycoprotein , chemotherapy , medicine , vinca , biology , pharmacology , drug resistance , microbiology and biotechnology , cyclophosphamide , multiple drug resistance , genetics , calcium
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 colchin, 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 IC 50 s. 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 phenotyic properties of the U‐937 cell line, and that resistance modifier hypersensitivity was not associated with increase in pgp 170 expression.