RESISTANCE MECHANISMS IN MURINE TUMORS WITH ACQUIRED MULTIDRUG RESISTANCE

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:A1992JR29300024&DestLinkType=FullRecord&DestApp=WOS_CPL
Externe Identifier
  • Clarivate Analytics Document Solution ID: JR293
  • PubMed Identifier: 1445488
ISSN
0004-4172
Ausgabe der Veröffentlichung
9
Zeitschrift
ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH
Schlüsselwörter
  • GLUTATHIONE S-TRANSFERASE-PI
  • MULTIDRUG RESISTANCE
  • MURINE TUMORS
  • P-GLYCOPROTEIN
Paginierung
1163 - 1168
Datum der Veröffentlichung
1992
Status
Published
Titel
RESISTANCE MECHANISMS IN MURINE TUMORS WITH ACQUIRED MULTIDRUG RESISTANCE
Sub types
  • Article
Ausgabe der Zeitschrift
42-2

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
Mechanisms of multidrug resistance were studied in murine leukemia (L 1210) and sarcoma (Sa 180) tumors after pretreatment with anthracyclines in vivo. Despite identical pretreatment protocols, a considerable difference in the level of resistance between L 1210 and Sa 180 tumors was noted (for doxorubicin: 45-fold versus 340-fold; for daunorubicin: 51-fold versus 275-fold). However, no difference in mdr 1 gene-amplification and the overexpression of mdr 1-RNA or P-glycoprotein was demonstrated. None of these parameters did increase by further treatment with a higher concentration of anthracyclines. Resistant sublines of Sa 180 revealed an overexpression of glutathione S-transferase-pi (GST-pi) in comparison to the parental line, whereas in sensitive and resistant sublines of L 1210 tumors the expression of GST-pi was similar. In order to study whether trifluoperazine can reverse the P-glycoprotein mediated component of multidrug resistance, trifluoperazine and doxorubicin were tested in vitro in L 1210 and Sa 180 cells. In contrast to the complete reversal of resistance in L 1210 tumors, resistance in Sa 180 was only partly circumvented. However, by buthionine sulfoximine treatment, the toxicity of multidrug resistant Sa 180 tumors could be increased. It was possible to reverse the resistance of Sa 180 tumors completely by trifluoperazine plus buthionine sulfoximine. Thus, multidrug-resistant Sa 180 tumors express different defense mechanisms whereas L 1210 tumors express only one defense mechanism (P-glycoprotein).
Addresses
  • Department of Experimental Pathology, German Cancer Research Center, Heidelberg.
Autoren
eISSN
1616-7066
Externe Identifier
  • PubMed Identifier: 1445488
Open access
false
ISSN
0004-4172
Ausgabe der Veröffentlichung
9
Zeitschrift
Arzneimittel-Forschung
Schlüsselwörter
  • Tumor Cells, Cultured
  • Animals
  • Mice
  • Leukemia L1210
  • Sarcoma 180
  • Antineoplastic Agents
  • Blotting, Northern
  • Blotting, Southern
  • Immunohistochemistry
  • Drug Resistance
Sprache
eng
Medium
Print
Paginierung
1163 - 1168
Datum der Veröffentlichung
1992
Status
Published
Datum der Datenerfassung
1992
Titel
Resistance mechanisms in murine tumors with acquired multidrug resistance.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
42

Data source: Europe PubMed Central

Abstract
Mechanisms of multidrug resistance were studied in murine leukemia (L 1210) and sarcoma (Sa 180) tumors after pretreatment with anthracyclines in vivo. Despite identical pretreatment protocols, a considerable difference in the level of resistance between L 1210 and Sa 180 tumors was noted (for doxorubicin: 45-fold versus 340-fold; for daunorubicin: 51-fold versus 275-fold). However, no difference in mdr 1 gene-amplification and the overexpression of mdr 1-RNA or P-glycoprotein was demonstrated. None of these parameters did increase by further treatment with a higher concentration of anthracyclines. Resistant sublines of Sa 180 revealed an overexpression of glutathione S-transferase-pi (GST-pi) in comparison to the parental line, whereas in sensitive and resistant sublines of L 1210 tumors the expression of GST-pi was similar. In order to study whether trifluoperazine can reverse the P-glycoprotein mediated component of multidrug resistance, trifluoperazine and doxorubicin were tested in vitro in L 1210 and Sa 180 cells. In contrast to the complete reversal of resistance in L 1210 tumors, resistance in Sa 180 was only partly circumvented. However, by buthionine sulfoximine treatment, the toxicity of multidrug resistant Sa 180 tumors could be increased. It was possible to reverse the resistance of Sa 180 tumors completely by trifluoperazine plus buthionine sulfoximine. Thus, multidrug-resistant Sa 180 tumors express different defense mechanisms whereas L 1210 tumors express only one defense mechanism (P-glycoprotein).
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/1445488
ISSN
0004-4172
Ausgabe der Veröffentlichung
9
Zeitschrift
Arzneimittelforschung
Schlüsselwörter
  • Animals
  • Antineoplastic Agents
  • Blotting, Northern
  • Blotting, Southern
  • Drug Resistance
  • Immunohistochemistry
  • Leukemia L1210
  • Mice
  • Sarcoma 180
  • Tumor Cells, Cultured
Sprache
eng
Country
Germany
Paginierung
1163 - 1168
Datum der Veröffentlichung
1992
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
1992
Titel
Resistance mechanisms in murine tumors with acquired multidrug resistance.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
42

Data source: PubMed

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