Document Detail


Increase of daunorubicin and vincristine accumulation in multidrug resistant human ovarian carcinoma cells by a monoclonal antibody reacting with P-glycoprotein.
MedLine Citation:
PMID:  2898943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An overexpression of plasma membrane 170-180 kDa P-glycoproteins is consistently found in multidrug-resistant (MDR) cell lines. In this study MRK-16, a monoclonal antibody (mAb) reacting with P-glycoprotein is used to study the putative functional role of this protein in vincristine (VCR) and daunorubicin (DNR) cellular accumulation in the MDR human ovarian carcinoma cell line 2780AD. We established that this cell line is highly cross-resistant to vincristine and daunomycin, related to a greatly reduced drug accumulation. Verapamil (Vp) (8 microM) caused a 3.6-fold increase in DNR as well as VCR accumulation. Exposition of 2780AD cells to MRK-16 led to an increase of 30% in cellular accumulation of VCR, both in normal growth medium as well as in medium without added glucose and with sodium azide, which largely depleted cellular ATP levels. No increase in DNR accumulation was found under these conditions. However, in the presence of 8 microM Vp, MRK-16 increased not only VCR but also DNR accumulation with about 30%. The relative increase of DNR accumulation was constant in a concentration range of 0.2-4 microM DNR. These data indicate that mAbs against P-glycoprotein might potentiate the action of calcium antagonists like Vp to increase cellular anthracycline accumulation.
Authors:
H J Broxterman; C M Kuiper; G J Schuurhuis; T Tsuruo; H M Pinedo; J Lankelma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  37     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1988 Jun 
Date Detail:
Created Date:  1988-07-29     Completed Date:  1988-07-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2389-93     Citation Subset:  IM    
Affiliation:
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / immunology*
Calcium Channel Blockers / pharmacology
Daunorubicin / metabolism*
Drug Resistance
Female
Humans
Membrane Glycoproteins / immunology,  physiology*
Ovarian Neoplasms / metabolism
P-Glycoprotein
Tumor Cells, Cultured / metabolism
Vincristine / metabolism*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Calcium Channel Blockers; 0/Membrane Glycoproteins; 0/P-Glycoprotein; 20830-81-3/Daunorubicin; 57-22-7/Vincristine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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