Linked Life Data

10856431

Source:http://linkedlifedata.com/resource/pubmed/id/10856431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-7-13
pubmed:abstractText
An Ehrlich ascites tumour cell line (EHR2) was selected in vivo for resistance to mitoxantrone (MITOX). The resistant cell line (EHR2/MITOX) was 6123-, 33-, and 30-fold-resistant to mitoxantrone, daunorubicin, and etoposide, respectively, but retained sensitivity to vincristine. The resistant cells showed moderate sensitisation to mitoxantrone on treatment with verapamil or cyclosporin A. Compared with EHR2, the multidrug resistance-associated protein mRNA was increased 13-fold in EHR2/MITOX. Western blot analysis showed an unchanged, weak expression of P-glycoprotein. Topoisomerase IIalpha was reduced to one-third in EHR2/MITOX relative to EHR2 cells, whereas topoisomerase IIbeta was present in EHR2 but could not be detected in EHR2/MITOX. In the resistant subline, net accumulation of MITOX (120 min) and daunorubicin (60 min) was reduced by 43% and 27%, respectively, as compared with EHR2. The efflux of daunorubicin from preloaded EHR2/MITOX cells was significantly increased. EHR2/MITOX microsomes had a significant basal unstimulated ATPase activity. The apparent K(i) value for vanadate inhibition of the ATPase activity in EHR2/MITOX microsomes was not significantly different from the K(i) value for P-glycoprotein-positive cells. However, whereas verapamil (50 microM) inhibited the ATPase activity of EHR2/MITOX microsomes, it stimulated the ATPase activity of microsomes derived from P-glycoprotein-positive cells. In conclusion, the resistance in EHR2/MITOX was multifactorial and appeared to be associated with: 1) a quantitative reduction in topoisomerase IIalpha and beta protein; 2) reduced drug accumulation, probably as a result of increased expression of a novel transport protein with ATPase activity; and 3) increased expression of MRP mRNA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
363-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10856431-ATP-Binding Cassette Transporters, pubmed-meshheading:10856431-Adenosine Triphosphatases, pubmed-meshheading:10856431-Animals, pubmed-meshheading:10856431-Antineoplastic Agents, pubmed-meshheading:10856431-Biological Transport, pubmed-meshheading:10856431-Carcinoma, Ehrlich Tumor, pubmed-meshheading:10856431-DNA Topoisomerases, Type II, pubmed-meshheading:10856431-Daunorubicin, pubmed-meshheading:10856431-Drug Resistance, Multiple, pubmed-meshheading:10856431-Drug Resistance, Neoplasm, pubmed-meshheading:10856431-Immunoassay, pubmed-meshheading:10856431-Mice, pubmed-meshheading:10856431-Mitoxantrone, pubmed-meshheading:10856431-Multidrug Resistance-Associated Proteins, pubmed-meshheading:10856431-P-Glycoprotein, pubmed-meshheading:10856431-Subcellular Fractions, pubmed-meshheading:10856431-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Characterisation of non-P-glycoprotein multidrug-resistant Ehrlich ascites tumour cells selected for resistance to mitoxantrone.
pubmed:affiliation
Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. dln@dadlnet.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't