Linked Life Data

7756675

Source:http://linkedlifedata.com/resource/pubmed/id/7756675

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-6-26
pubmed:abstractText
In the present study we investigated the effectiveness of 14, 15 and 18 nucleotide antisense phosphorothioate oligonucleotides (S-ODNs) directed to four different regions of the published mdr-1 gene sequence to reduce the level of mdr-1 gene product (p170, P-glycoprotein) and its function in the over-expressing cell lines Lo-VoDxR, S180DxR and KBChR8-5. The highest efficiency in reduction of multiple drug resistance was obtained at a concentration of 2 microM. In proliferation assays a growth reduction of 50% was observed after exposure of doxorubicin-resistant cells to S-ODN3. p170 protein expression of the resistant cell line LoVoDxR was reduced to the level of the sensitive cell line LoVo as shown by Western blot analysis. S-ODN3 reduced the ID50 of the two human cell lines up to 60% (LoVoDxR) and 21% (KBChR8-5), respectively, but showed no effect in the murine cell line S180DxR. In contrast, S-ODN1 was most effective in the murine system (67% reduction of the ID50), less effective in LoVoDxR (34%) and exhibited no effect in cell line KBChR8-5. Based on the results with the antisense oligonucleotides, a ribozyme directed against the mRNA target region of S-ODN3 was designed. This ribozyme was able to reduce the mdr-1 mRNA in total RNA preparations from cell line LoVoDxR up to 80% after an incubation time of 6 h in the presence of 10 mM MgCl2 at pH 7.5. A modified ribozyme was investigated in cell culture and reduced chemo-resistance of the resistant cell line LoVoDxR and ex vivo cultured blasts of acute myeloid leukemia patients up to 50%.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0959-4973
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
124-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Reversal of multiple drug resistance in vitro by phosphorothioate oligonucleotides and ribozymes.
pubmed:affiliation
Department of Hematology/Oncology, University Clinics, Göttingen, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't