Linked Life Data

17662692

Source:http://linkedlifedata.com/resource/pubmed/id/17662692

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-8-7
pubmed:abstractText
Overexpression of MDR-1 represents a critical mechanism of drug resistance in cancer. Proteasome inhibitors recently entered the clinic for treatment of multiple myeloma. We provide evidence that the proteasome-inhibitors Bortezomib and MLN273 are both substrates of MDR-1 by using knockdown of MDR-1 via a transposon-based vector system stably expressing siRNA against MDR-1 in MDR-1-overexpressing K562/Dox cells. Notably, the efficacy of MLN273 (EC(50) from 253 ng/ml in MDR-1(+) to 9.7 ng/ml in MDR-1(-) cells) was much more dependent on MDR-1 expression than Bortezomib (EC(50) from 24.9 ng/ml in MDR-1(+) to 4.5 ng/ml in MDR-1(-) cells). Growth inhibition in MDR-1 negative cells was in part due to increased rate of apoptosis. The enhanced inhibitory effect on the proteasome by loss of MDR-1 was corroborated by a reduced proteasomal activity. Our report provides evidence that MLN273 and, to a lesser degree, Bortezomib are both MDR-1-substrates, which might be relevant for drug-resistance in cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
361
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-54
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Knockdown of PgP resensitizes leukemic cells to proteasome inhibitors.
pubmed:affiliation
Laboratory of Molecular Genetics, Department of Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria.
pubmed:publicationType
Journal Article