Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model

초록

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.

키워드