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https://doi.org/10.3748/wjg.v18.i27.3527
Title: | Polo-like kinase 1, a new therapeutic target in hepatocellular carcinoma | Authors: | Mok, W.C. Wasser, S. Tan, T. Lim, S.G. |
Keywords: | Apoptosis Endonuclease G Forkhead box transcription factors Nude mice Polo-like kinase 1 RNA |
Issue Date: | 21-Jul-2012 | Citation: | Mok, W.C., Wasser, S., Tan, T., Lim, S.G. (2012-07-21). Polo-like kinase 1, a new therapeutic target in hepatocellular carcinoma. World Journal of Gastroenterology 18 (27) : 3527-3536. ScholarBank@NUS Repository. https://doi.org/10.3748/wjg.v18.i27.3527 | Abstract: | 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-7 cells 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 a reduction 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. © 2012 Baishideng. | Source Title: | World Journal of Gastroenterology | URI: | http://scholarbank.nus.edu.sg/handle/10635/109521 | ISSN: | 10079327 | DOI: | 10.3748/wjg.v18.i27.3527 |
Appears in Collections: | Staff Publications |
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