IkappaB Kinase epsilon (IKKepsilon) is a member of the IKK family which plays an important role in the activation of nuclear factor-kappaB (NF-kappaB). Overexpressed in over 30% of breast cancers, IKKepsilon has been recently identified as a potential breast cancer oncogene. The purpose of this study is to examine the therapeutic potential of IKKepsilon siRNA on human breast cancer cells.

Eight siRNAs targeting different regions of the IKKepsilon mRNA were designed, and the silencing effect was screened by quantitative real time RT-PCR. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth(via soft agar assay), cell cycle arrest, apoptosis (via annexing binding), NF-kappaB basal level, and NF-kappaB related gene expressions upon the IKKepsilon silencing.

Silencing of IKKepsilon in human breast cancer cells resulted in decrease of focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of IKKepsilon suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of IKKepsilon siRNA was mediated by arresting cells in G0/G1 phase, which was caused by down-regulation of cyclin D1. Furthermore, we demonstrated that silencing of IKKepsilon inhibited the NF-kappaB basal activity as well as the Bcl-2 expression. Significant apoptosis was not observed in breast cancer cells upon the silencing of IKKepsilon. The present study provided the first evidence that silencing IKKepsilon using synthetic siRNA could inhibit the invasiveness properties and proliferation of breast cancer cells.

Our results suggested that silencing IKKepsilon using synthetic siRNA may offer a novel therapeutic strategy for breast cancer.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.