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Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer

Cancer Gene Therapy volume 11, pages 748–756 (2004)Cite this article

Abstract

RNA interference technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Here our results showed that hdm2-siRNA silenced its target mRNA specifically and effectively in human breast cancer cells, reduced tumor cell proliferation and induced apoptotic cell death. Other molecular features modified by hdm2-siRNA included decreased Bcl-2, NF-κB, survivin, Ras and Raf levels, elevated p53, p21, BRCA1, Bax, and caspase levels as well as altered expression of other genes. hdm2-siRNA also caused cell cycle arrest at G1 phases with reduction in cyclin and Cdk proteins. In addition, hdm2-siRNA displayed in vivo antitumor activity and increased therapeutic effectiveness of mitomycin in MCF-7 xenografts. Thus, hdm2-siRNA may be a promising gene-specific drug for the treatment of human breast cancer and other tumors.

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Acknowledgements

This work was supported in part by NSFC Grants (No. 30025043, 30271514), the National 863 and 973 Program Grants (No. 2002AA214021, 2002CB513108), and a grant from National Foundation for Cancer Research (USA).

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Authors and Affiliations

  1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100050, China

    Tie-gang Liu, Bo-yang Shang, Zhang Min, Hong-wei He, Jian-ming Jiang, Yong-su Zhen & Rong-guang Shao

  2. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    James Q Yin & Fang Chen

  3. AltCures Pharmaceutical Inc., Boston, 02124, MA, USA

    James Q Yin

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  1. Tie-gang Liu
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Correspondence to James Q Yin or Rong-guang Shao.

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Liu, Tg., Yin, J., Shang, By. et al. Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer. Cancer Gene Ther 11, 748–756 (2004). https://doi.org/10.1038/sj.cgt.7700753

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