Reversal of drug sensitivity in MDR subline of P388 leukemia by gene-targeted antisense oligonucleotide.
J Pharm Sci
; 84(10): 1205-9, 1995 Oct.
Article
em En
| MEDLINE
| ID: mdl-8801335
ABSTRACT
We attempted to reverse multidrug resistance (MDR) by treatment with 25-mer antisense phosphorothioate oligonucleotide. The phosphorothioate analogs, the sequences of which are sense or antisense to the initiation codon of mouse mdr1 mRNA, were tested against murine leukemic P388/S and adriamycin-resistant P388/ADR cell lines. A weak inhibitory effect on the growth of P388/S and P388/ADR cells was observed at a sense and antisense oligonucleotide concentration of 30 microM. Using the monoclonal antibody to P-glycoprotein and a flow cytometry technique, we showed that the level of expression of P-glycoprotein in P388/ADR cells treated with antisense oligonucleotide was lower than when treated with sense oligonucleotide. The antisense oligonucleotide potentiated the growth-inhibitory effect of vinblastine on P388/ADR cells, whereas sense oligonucleotide did not. This was accompanied by an increase in vinblastine retention in the cells. The reversal of the resistance by antisense oligonucleotide was increased by the combination with 1 microM verapamil. These results suggest that the antisense oligonucleotide and low dose verapamil may be useful in circumventing the resistance to anticancer drugs of MDR tumors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tionucleotídeos
/
Leucemia P388
/
Oligonucleotídeos Antissenso
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Japão