Silencing of IKKε using siRNA inhibits proliferation and invasion of glioma cells in vitro and in vivo

Recent studies implicated IKK epsilon in the pathogenesis of many human cancers by promoting cell proliferation, increasing tumor angiogenesis and metastasis, and generating resistance to cell apoptosis. However, whether IKK epsilon can influence the invasive ability and proliferation of glioma cells remains largely unknown. In this study, we showed that overexpression of IKK epsilon is positively correlated to glioma pathological grade, suggesting that IKK epsilon plays a role in tumor progression, rather than tumor initiation. Targeted knockdown of IKK epsilon in human glioma cells using siRNA, was associated with inhibition of cell growth, cell cycle arrest and decreased cell invasion; however, notable apoptosis was not observed. Furthermore, we demonstrated that transposition of NF-kappa B p65 resulted in the alteration of these phenotypes. Tumor growth was attenuated in established subcutaneous gliomas in nude mice treated with IKK epsilon siRNA in vivo. Collectively, our results suggest that deregulation of IKK epsilon plays a pivotal role in the uncontrolled proliferation and malignant invasion of glioma cells in vitro and in vivo by targeting NF-kappa B. Silencing of IKK epsilon using synthetic siRNAs may offer a novel therapeutic strategy for the treatment of glioma.