title: Downregulation of PGY1/MDR1 mRNA level in human KB cells by antisense oligonucleotide conjugates. RNA accessibility in vitro and intracellular antisense activity.
abstract: Inhibition of PGY1/MDR1 (multidrug resistance gene 1) mRNA expression in multidrug resistant KB-8-5 cells by 5'-bis-pyrenyl-3'-aminohexyl oligodeoxyribonucleotide conjugates targeted to four sites of this mRNA has been investigated. Three of the tested oligonucleotide conjugates specifically inhibited the expression of PGY1/MDR1 mRNA as monitored by the RT-PCR assay. The oligonucleotide conjugate targeted to the region (+178; +194) of the PGY1/MDR1 mRNA decreased level of this mRNA to 10% compared to the control. Nuclease-resistant analogs of oligonucleotide, complementary to this MDR1 mRNA region therefore, might be considered as a prototype compounds for development of gene-targeted therapeutic agents for overcoming the MDR phenotype caused by the overexpression of the PGY1/MDR1 gene.
authors.affiliation: Institute of Bioorganic Chemistry Siberian Division, Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk-90, 630090, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kostenko
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Laktionov
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger