首页|Polo-like kinase 1, a new therapeutic target in hepatocellular carcinoma

Polo-like kinase 1, a new therapeutic target in hepatocellular carcinoma

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AIM:To investigate the role of polo-like kinase 1 (PLK1)as a therapeutic target for hepatocellular carcinoma (HCC).METHODS:PLK1 gene expression was evaluated in HCC tissue and HCC cell lines.Gene knockdown with short-interfering RNA (siRNA) was used to study PLK1 gene and protein expression using real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting,and cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2H-tetrazolium (MTS) and bromodeoxyuridine(BrdU) assays.Apoptosis was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay,and caspase-inhibition assay.Huh-7cells were transplanted into nude mice and co-cultured with PLK1 siRNA or control siRNA,and tumor progression was compared with controls.RESULTS:RT-PCR showed that PLK1 was overexpressed 12-fold in tumor samples compared with controls,and also was overexpressed in Huh-7 cells.siRNA against PLK1 showed a reduction in PLK1 gene and protein expression of up to 96％ in Huh-7 cells,and areduction in cell proliferation by 68％ and 92％ in MTS and BrdU cell proliferation assays,respectively.There was a 3-fold increase in apoptosis events,and TUNEL staining and caspase-3 assays suggested that this was caspase-independent.The pan-caspase inhibitor Z-VAD-FMK was unable to rescue the apoptotic cells.Immnofluorescence co-localized endonuclease-G to fragmented chromosomes,implicating it in apoptosis.Huh-7 cells transplanted subcutaneously into nude mice showed tumor regression in siPLK1-treated mice,but not in controls.CONCLUSION:Knockdown of PLK1 overexpression in HCC was shown to be a potential therapeutic target,leading to apoptosis through the endonuclease-G pathway.

RNAPolo-like kinase 1ApoptosisEndonuclease GForkhead box transcription factorsNude mice

Wei Chuen Mok、Shanthi Wasser、Theresa Tan、Seng Gee Lim

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Institute of Molecular and Cell Biology, Agency for Science, Technology and Research,Singapore 138673, Singapore

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

Department of Gastroenterology and Hepatology, Yong Loo Lin School of Medicine, National University Health System, Singapore 117597, Singapore

Department of Medicine, National University of Singapore, Singapore 119074, Singapore

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National University of Singapore GrantsNational University of Singapore Grants

R-172-000-001-731R-172-000-024-731

2012

10.3748/wjg.v18.i27.3527

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(27)
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