Blocking IKKα expression inhibits prostate cancer invasiveness

Pharm Res. 2011 Jun;28(6):1357-69. doi: 10.1007/s11095-010-0351-z. Epub 2010 Dec 30.


Purpose: IKKα has been recently identified as a key mediator of the inflammation and metastasis in prostate cancer. In the present study, we intend to silence the IKKα expression in prostate cancer cells using synthetic siRNAs and examine their biological effects on tumor cell invasiveness and growth.

Methods: Three synthetic siRNAs targeting different regions of the IKKα mRNA were designed, and the silencing effect was determined in PC-3 and DU145 cells. Numerous studies, including wound-healing assay, migration assay, invasion assay, cell attachment assay, cell proliferation, and cell cycle analysis, were conducted to investigate the biological effects of the IKKα siRNAs on prostate cancer cells.

Results: We have identified potent siRNAs that can silence the IKKα up to 74%. Inhibition of IKKα reduced the wound healing, migration, invasion and cell attachment capabilities of prostate cancer cells. Similar anti-invasive effects were also observed in the presence of RANKL. However, silencing of IKKα only showed a negligible effect on cell proliferation and cell cycle distribution.

Conclusion: This study presents compelling evidence that IKKα plays a major role in prostate cancer invasion and metastasis, but not in cell proliferation. Silencing of IKKα with siRNA may therefore provide a promising therapeutic strategy for prostate cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / biosynthesis
  • I-kappa B Kinase / genetics
  • Male
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics


  • RNA, Small Interfering
  • I-kappa B Kinase