title: Delivery of DNAzyme targeting aurora kinase A to inhibit the proliferation and migration of human prostate cancer.
abstract: Herein, a polyethylenimine derivative N-acetyl-L-leucine-polyethylenimine (N-Ac-L-Leu-PEI) was employed as a carrier to achieve the delivery of DNAzyme targeting aurora kinase A using PC-3 cell as a model. Flow cytometry and confocal laser scanning microscopy demonstrated that the derivative could realize the cellular uptake of nanoparticles in an energy-dependent and clathrin-mediated pathway and obtain a high DNAzyme concentration in the cytoplasm through further endosomal escape. After DNAzyme transfection, expression level of aurora kinase A would be downregulated at the protein level. Meanwhile, the inhibition of cell proliferation was observed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell colony formation assay, attributing to the activation of apoptosis and cell cycle arrest. Through flow cytometric analysis, an early apoptotic ratio of 25.93% and G2 phase of 22.58% has been detected after N-Ac-L-Leu-PEI-mediated DNAzyme transfection. Finally, wound healing and Transwell migration assay showed that DNAzyme transfection could efficiently inhibit the cell migration. These results demonstrated that N-Ac-L-Leu-PEI could successfully mediate the DNAzyme delivery and downregulate the expression level of aurora kinase A, triggering a significant inhibitory effect of excessive proliferation and migration of tumor cells.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Sai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Haobo
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Clinic Library, Changchun Women and Children's Health, Changchun, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D021881:DNA, Catalytic / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D021881:DNA, Catalytic; D011094:Polyethyleneimine; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: DNAzyme; N-acetyl-l-leucine-polyethylenimine; aurora kinase A; cell migration; cell proliferation; gene therapy