Linked Life Data

17611700

Source:http://linkedlifedata.com/resource/pubmed/id/17611700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-7-5
pubmed:abstractText
Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The 'classical' MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers. Recent developments in the use of small interfering RNAs for specific inhibition of gene expression have highlighted their potential use as therapeutic agents. DNA cassettes encoding RNA polymerase III promoter-driven siRNA-like short hairpin RNAs (shRNAs) allow long-term expression of therapeutic RNAs in targeted cells. A variety of viral vectors have been used to deliver such cassettes to mammalian cells. In this study, the construction of different adenoviruses for anti-MDR1/P-gp shRNA delivery in different human multidrug-resistant cancer cells was investigated. The efficiency of the shRNAs was compared to adenoviral delivery of an anti-MDR1/P-gp ribozyme construct. It could be demonstrated that MDR1/P-gp mRNA and protein expression could be completely inhibited by adenoviral delivery of anti-MDR1/P-gp shRNAs. This downregulation in mRNA and protein expression was accompanied by a complete inhibition of the pump activity of MDR1/P-gp and a reversal of the multidrug-resistant phenotype. By application of adenoviral encoded anti-MDR1/P-gp ribozyme construct merely weak effects on gene expression were observed. In conclusion, the data demonstrate that adenoviral delivery of shRNAs can chemosensitize human cancer cells, that adenoviral delivery of shRNAs is much more effective than adenoviral delivery of ribozymes, and that adenovirus-based vectors can be very effective agents for efficient delivery of therapeutic RNA molecules.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
419-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Overcoming the classical multidrug resistance phenotype by adenoviral delivery of anti-MDR1 short hairpin RNAs and ribozymes.
pubmed:affiliation
Institute of Pathology, Charité Campus Mitte, Humboldt University Berlin, D-10117 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't