Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model
- Authors
- Oh, Binna; Song, Hojung; Lee, Dahee; Oh, Jungju; Kim, Gyeungyun; Ihm, Sung-Hee; Lee, Minhyung
- Issue Date
- Feb-2017
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- Antisense-oligodeoxynucleotide; microRNA-21; R3V6 peptide; glioblastoma; gene therapy
- Citation
- JOURNAL OF DRUG TARGETING, v.25, no.2, pp.132 - 139
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DRUG TARGETING
- Volume
- 25
- Number
- 2
- Start Page
- 132
- End Page
- 139
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4815
- DOI
- 10.1080/1061186X.2016.1207648
- ISSN
- 1061-186X
- 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 (25kDa, 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.
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