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Blocking IKKα Expression Inhibits Prostate Cancer Invasiveness

Pharmaceutical Research volume 28, pages 1357–1369 (2011)Cite this article

ABSTRACT

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.

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ACKNOWLEDGMENTS

This project has been supported by a grant (1R21CA143683-01) from the National Cancer Institute at NIH. We also would like to express thanks for the financial support from a start-up package at the University of Missouri-Kansas City.

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Affiliations

  1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA

    Rubi Mahato, Bin Qin & Kun Cheng

Authors
  1. Rubi Mahato
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  2. Bin Qin
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  3. Kun Cheng
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Corresponding author

Correspondence to Kun Cheng.

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Mahato, R., Qin, B. & Cheng, K. Blocking IKKα Expression Inhibits Prostate Cancer Invasiveness. Pharm Res 28, 1357–1369 (2011). https://doi.org/10.1007/s11095-010-0351-z

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  • DOI: https://doi.org/10.1007/s11095-010-0351-z

KEY WORDS

  • IKKα
  • invasiveness
  • prostate cancer
  • siRNA
  • RANKL