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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.

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 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.
AuthorsJ Botling, G Liminga, R Larsson, P Nygren, K Nilsson
JournalInternational journal of cancer (Int J Cancer) Vol. 58 Issue 2 Pg. 269-74 (Jul 15 1994) ISSN: 0020-7136 [Print] United States
PMID7913083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, Surface
  • Carrier Proteins
  • Membrane Glycoproteins
  • Vincristine
  • Cyclosporine
  • Verapamil
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, Surface (physiology)
  • Carrier Proteins (physiology)
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Cyclosporine (pharmacology)
  • Drug Interactions
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Humans
  • Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
  • Membrane Glycoproteins (physiology)
  • Tumor Cells, Cultured
  • Verapamil (pharmacology)
  • Vincristine (pharmacology)

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