Document Detail


Cyclosporin A, verapamil and S9788 reverse doxorubicin resistance in a human medullary thyroid carcinoma cell line.
MedLine Citation:
PMID:  7756676     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multidrug resistance was investigated in TT cells, a human medullary thyroid carcinoma (MTC) cell line and in normal thyrocytes. MDR1 mRNA was revealed by polymerase chain reaction (PCR) analysis both in normal and neoplastic cells despite the absence of glycoprotein P (Pgp) by immunohistochemistry using JSB-1 monoclonal antibody. Glutathione-S-transferase mRNA was undetectable by Northern blotting in TT cells. Doxorubicin-induced cytotoxicity was evaluated in TT cells with MTT, lacticodehydrogenase (LDH), glutathione (GSH) assays and neutral red uptake. IC50 values obtained for MTT assays were higher than those obtained with the three other tests. Cyclosporin A (CSA) (3 microM), verapamil (10 microM) and S9788 (5 microM) partially reversed the resistance to doxorubicin after a 48 h co-incubation (followed by a 24 h post-incubation for the S9788). Under these conditions, GSH levels were altered by verapamil and S9788, whereas CSA decreased LDH activity. CSA and verapamil had no effect on MTT assay. In conclusion this MTC cell line exhibited over-expression of the MDR1 gene and its resistance to doxorubicin can be partially reversed by CSA, verapamil and S9788.
Authors:
C Massart; J Gibassier; M Raoul; P Pourquier; G Leclech; J Robert; C Lucas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  6     ISSN:  0959-4973     ISO Abbreviation:  Anticancer Drugs     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-06-26     Completed Date:  1995-06-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  135-46     Citation Subset:  IM    
Affiliation:
Laboratoire de Biochimie A, CHU de Pontchaillou, Rennes, France.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Medullary / drug therapy*,  pathology
Cyclosporine / pharmacology*
Doxorubicin / pharmacology*
Drug Resistance, Multiple* / genetics
Drug Synergism
Glutathione / metabolism
Glutathione Transferase / biosynthesis,  genetics
Humans
Neoplasm Proteins / biosynthesis,  genetics*
P-Glycoprotein / biosynthesis,  genetics*
Piperidines / pharmacology*
Polymerase Chain Reaction
RNA, Messenger / biosynthesis
RNA, Neoplasm / biosynthesis
Thyroid Neoplasms / drug therapy*,  pathology
Triazines / pharmacology*
Verapamil / pharmacology*
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/P-Glycoprotein; 0/Piperidines; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Triazines; 140945-01-3/S 9788; 23214-92-8/Doxorubicin; 52-53-9/Verapamil; 59865-13-3/Cyclosporine; 70-18-8/Glutathione; EC 2.5.1.18/Glutathione Transferase

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


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