title: Down-Regulation of MRP1 Expression in C6/VP16 Cells by Chitosan-MRP1-siRNA Nanoparticles.
abstract: High expression of multidrug resistance-associated protein 1 (MRP1) in tumor cells reduces effectiveness of chemotherapy drugs. In this study, we screened MRP1 interfering RNA (MRP1-siRNA) molecules that are able to reverse etoposide (VP16) resistance in multidrug resistance rat glioma cell line C6/VP16, and identified one siRNA molecule that is able to effectively deplete the expression of MRP1 gene and reverse tumor cells resistance to etoposide. Since siRNA instability limits its application in treatment of diseases, we next tested silencing effect of chitosan-MRP1-siRNA nanoparticles and found that the nanoparticles with N:P ratio 175 are able to effectively inhibit MRP1 mRNA and protein expression. Our data demonstrate that chitosan can be used as siRNA carrier for high efficient gene silencing in tumor cells.
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China. huang_shulan@163.com.
authors.forename: Shulan
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D014162:Transfection
chemical_list: D048271:Chitosan; D005047:Etoposide; D008055:Lipids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; C086724:Lipofectamine; C421109:multidrug resistance-associated protein 1
keywords: Etoposide; Multidrug resistance-associated protein 1; Rat glioma cells; Small interfering RNA