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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / genetics
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / metabolism*
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cell Survival / genetics
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Drug Delivery Systems
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Gene Silencing / drug effects
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Hep G2 Cells
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Humans
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Liposomes
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Mice
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Mice, Nude
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Polo-Like Kinase 1
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism*
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RNA, Small Interfering / administration & dosage*
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RNA, Small Interfering / genetics*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Liposomes
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Protein Serine-Threonine Kinases