title: Intravenous liposomal delivery of the short hairpin RNAs against Plk1 controls the growth of established human hepatocellular carcinoma.
abstract: Polo-like kinase 1 (Plk1) is a key cell cycle regulator that is frequently overexpressed in human hepatocellular carcinomas. Blockade of the Plk1 pathway has been reported to be capable of inducing anti-tumor effect. Here, plasmids containing U6 promoter-driven shRNAs against human Plk1 were constructed and transfected in human hepatocellular carcinoma cell line HepG2. ShRNA targeting Plk1 almost completely reduced Plk1 expression in HepG2 hepatocellular carcinoma cells, as confirmed by RT-PCR and Western blot. As a consequence, HepG2 cells exhibited reduced proliferation and enhanced apoptosis in vitro. Most importantly, Treatment with Plk shRNA-DOTAP:Chol complex significantly suppressed the growth of HepG2 xenografts, accompanied with phenotypic changes in tumor cells, including proliferation inhibition and apoptosis induction. Our study suggested that shRNA-mediated silencing of Plk1 might be a novel therapeutic approach against human hepatocellular carcinoma by inhibiting tumor cells proliferation and inducing apoptosis.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China. denghongx@scu.edu.cn
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Ma
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016503:Drug Delivery Systems; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008081:Liposomes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1