title: Silencing of PDK1 gene expression by RNA interference suppresses growth of esophageal cancer.
abstract: The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantation, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P<0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P<0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.
authors.affiliation: Department of Pathology, First Affiliated Hospital of Zhengzhou University and Henan Key Laboratory for Tumor Pathology, Zhengzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Kui-Sheng
authors.initials: KS
authors.lastname: Chen
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; C578564:Pdpk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt