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The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines

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Summary

The activity of the histone deacetylase inhibitor PXD101 was investigated in three hepatocellular carcinoma (HCC) cell lines. PXD101was found to inhibit cell growth at a dose-dependent manner and induce histone acetylation in PLC/PRF/5, Hep3B and HepG2 cells. In PLC/PRF/5 and Hep3B cells which express hepatitis B-related genes (HBx, HBc and HBc), treatment with PXD101 resulted in apoptosis without a significant effect on viral gene expression. Exposure to PXD101 for up to 48 h had varying effects on the expression of 12 cellular genes with tumor suppressor functions, including p21, SOCS1, CMTM5, RASAL1, DLEC1, SFRP (-1, -2, -4 and -5), ADAMTS (-8 and -9). This study provided the basis for a phase II clinical trial of PXD101 in inoperable hepatitis-B associated HCC.

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Acknowledgements

This study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (Bethesda, USA). Result of this study was presented as a poster at the 98th American Association of Cancer Research annual meeting in April 2007, Los Angeles; abstract number 2494. This study was funded by the Direct Grant of the Chinese University of Hong Kong (Reference 2005.1.018), and the Li Ka Shing Institute for Health Sciences.

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Authors and Affiliations

  1. State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

    Brigette B.Y. Ma, Fion Sung, Qian Tao, Fan Fong Poon, Vivian W. Lui, Winnie Yeo, Stephen L. Chan & Anthony T.C. Chan

  2. Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China

    Brigette B.Y. Ma

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  1. Brigette B.Y. Ma
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Correspondence to Brigette B.Y. Ma.

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Ma, B.B., Sung, F., Tao, Q. et al. The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs 28, 107–114 (2010). https://doi.org/10.1007/s10637-009-9219-7

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