title: Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model.
abstract: MicroRNA-21 (miR-21) expression in glioblastoma inhibits the expression of pro-apoptotic genes, thereby promoting tumor growth. A previous study showed that the amphiphilic R3V6 peptide is an efficient carrier of the anti-miR-21 antisense oligodeoxynucleotide (antisense-ODN) into cells in vitro. In the current study, in vivo delivery of antisense-ODN using the R3V6 peptide was evaluated in a glioblastoma animal model. In vitro transfection showed that the R3V6 peptide delivered antisense-ODN more efficiently than polyethylenimine (25 kDa, PEI25k) in C6 glioblastoma cells. For in vivo evaluation, antisense-ODN/R3V6 complex was injected intratumorally into a C6 glioblastoma xenograft animal model. Tumor growth was suppressed by the injection of the antisense-ODN/R3V6 complex, compared with the antisense-ODN/PEI25k and scrambled-antisense-ODN (scr-antisense-ODN)/R3V6 complexes. Real-time RT-PCR showed that miR-21 levels were reduced most efficiently by the antisense-ODNR3V6 complex in tumors. Due to inhibition of miR-21, expression of the programed cell death 4 (PDCD4) gene was promoted in tumors, resulting in the induction of apoptosis of tumor cells. These results suggest that delivery of antisense-ODN using R3V6 peptides may be useful for the development of antisense-ODN therapy for glioblastoma.
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Binna
authors.initials: B
authors.lastname: Oh
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Hojung
authors.initials: H
authors.lastname: Song
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Dahee
authors.initials: D
authors.lastname: Lee
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Jungju
authors.initials: J
authors.lastname: Oh
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Gyeungyun
authors.initials: G
authors.lastname: Kim
authors.affiliation: b Department of Internal Medicine , Hallym University College of Medicine , Chuncheon , Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Ihm
authors.affiliation: a Department of Bioengineering , College of Engineering, Hanyang University , Seoul , Korea.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D010455:Peptides; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C114487:PDCD4 protein, human; D010455:Peptides; D016601:RNA-Binding Proteins
keywords: Antisense-oligodeoxynucleotide; R3V6 peptide; gene therapy; glioblastoma; microRNA-21