title: Interaction between cyclooxygenase-2, Snail, and E-cadherin in gastric cancer cells.
abstract: OBJECTIVE
  To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E-cadherin in gastric cancer cells.
  
  
  METHODS
  COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-κB specific siRNA.
  
  
  RESULTS
  Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNA-mediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.
  
  
  CONCLUSIONS
  COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.
authors.affiliation: Xiao-Jun Liu, Zhao-Feng Chen, Hai-Long Li, Ze-Nan Hu, Ai-Ping Tian, Da Zhao, Yong-Ning Zhou, Liang Qiao, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Liu
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Li
authors.forename: Ze-Nan
authors.initials: ZN
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Tian
authors.forename: Da
authors.initials: D
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Cyclooxygenase-2; E-cadherin; Gastric cancer; Prostaglandin E2; celecoxib