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

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Abstract
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 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 phenotyic properties of the U-937 cell line, and that resistance modifier hypersensitivity was not associated with increase in pgp 170 expression.
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