title: Silencing of IKKε using siRNA inhibits proliferation and invasion of             glioma cells in vitro and in vivo.
abstract: Recent studies implicated IKKε in the pathogenesis of many human cancers             by promoting cell proliferation, increasing tumor angiogenesis and metastasis,             and generating resistance to cell apoptosis. However, whether IKKε can influence             the invasive ability and proliferation of glioma cells remains largely unknown.             In this study, we showed that overexpression of IKKε is positively correlated             to glioma pathological grade, suggesting that IKKε plays a role in tumor progression,             rather than tumor initiation. Targeted knockdown of IKKε 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-κB p65 resulted in the alteration of             these phenotypes. Tumor growth was attenuated in established subcutaneous gliomas             in nude mice treated with IKKε siRNA in vivo. Collectively, our results suggest             that deregulation of IKKε plays a pivotal role in the uncontrolled proliferation             and malignant invasion of glioma cells in vitro and in vivo by targeting NF-κB.             Silencing of IKKε using synthetic siRNAs may offer a novel therapeutic strategy             for the treatment of glioma.
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, PR China.
authors.forename: Huibing
authors.initials: H
authors.lastname: Li
authors.forename: Lingchao
authors.initials: L
authors.lastname: Chen
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic; D047368:Tumor Burden
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051550:I-kappa B Kinase