title: [Cholesterol-modified anti-MDR1 small interfering RNA: uptake and biological activity].
abstract: Small interfering RNAs (siRNA) are considered to be potent agents for specific gene silencing, but troubles in delivery of siRNA into cells limit their biomedical application. An accumulation of siRNA coupled with cholesterol residue at the 5'-end of the "passenger" strand (chol-siPHK) was investigated in HEK293, HepG2, SC1, and KB-8-5 cells. In the absence of a transfectant levels of both unmodified and chol-siRNAs were very low, whereas transfectant substantially increased transfection rate in all cell lines; in HEK293, SC1, and KB-8-5 cells transfection efficiency for the chol-siRNA being higher than that for the corresponding siRNA. Multiple drug resistance phenotype reversing activity of anti-MDR1-siRNAs targeted to the 557-577 region of MDR1 gene mRNA was investigated in KB-8-5 cancer cells. The chol-siRNA induced cancer cells' death in the presence of vinblastine doses tolerated before more effectively than the conventional siRNA did.
authors.forename: I S
authors.initials: IS
authors.lastname: Kruglova
authors.forename: M I
authors.initials: MI
authors.lastname: Meshchaninova
authors.forename: A G
authors.initials: AG
authors.lastname: Ven'iaminova
authors.forename: M A
authors.initials: MA
authors.lastname: Zenkova
authors.forename: V V
authors.initials: VV
authors.lastname: Vlasov
authors.forename: E L
authors.initials: EL
authors.lastname: Chernolovskaia
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol; D019008:Drug Resistance, Neoplasm; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014747:Vinblastine / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D014747:Vinblastine; D002784:Cholesterol