MicroRNA delivery system inhibits proliferation of androgen-independent prostate cancer

Abstract

Objective To prepare a microRNA(miRNA)delivery system using the branched polyethyleneimine(BPEI),linear polyethylenimine(LPEI)and polyamidoamine dendrimers(PAMAM)loaded with miRNA-15 aand miRNA-16-1,which can inhibit prostate cancer PC3 cell proliferation,and to examine the zeta potential,intracellular uptake,and the inhibition effect on PC3 cells of the three constructed nano-complexes.Methods Particle size analyzer was used to determine the size and potential of the three kinds of nano-complexes,and the miRNA affinity capability of them was determined by agarose gel electrophoresis retardation assay.The uptake efficiency of the nano-complexes by PC3 cells was examined by NC-miRNA labeled with FAM.CCK8 method was used to determine the inhibitory effect of the nano-complexes loaded with miRNA-15 a and miRNA-16-1against PC3 cells,and PCR was used to analyze their inhibitory effect on expression of Bcl-2,Cylin D1 and Wnt3agene in PC3 cells.Results BPEI,LPEI and PAMAM loaded with miRNA could form stable nano-complexes.When N/P=5,the intracellular uptake of BPEI/miRNA-FAM by PC3 cells was significantly higher than that of LPEI/miRNA-FAM and PAMAM/miRNA-FAM(P0.05).BPEI,LPEI and PAMAM could all carry miRNA-15 aand miRNA-16-1into PC3 cells and block Bcl-2,Cylin D1 and Wnt3aexpression in PC3 cells.Conclusion BPEI,LPEI and PAMAM loaded with miRNA-15 aand miRNA-16-1can suppress proliferation of prostate cancer PC3 cells and block Bcl-2,Cylin D1 and Wnt3aexpression.