title: COX-2 regulates E-cadherin expression through the NF-κB/Snail signaling pathway in gastric cancer.
abstract: Cyclooxygenase-2 (COX-2) participates in cancer invasion and metastasis by decreasing the expression of E-cadherin. However, the molecular mechanisms through which COX-2 regulates E-cadherin expression and function have not yet been fully elucidated. The aim of this study was to investigate the possible molecular mechanisms through which COX-2 regulates E-cadherin expression in gastric cancer. The mRNA and protein expression of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin was detected in gastric cancer cells by quantitative PCR and western blot analysis, respectively. The expression of these genes was also detected in healthy gastric mucosa and gastric cancer tissues by immunohistochemistry. We detected various levels of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin expression in the normal gastric mucosa and cancer tissues; however, the expression patterns differed: the increased expression of COX-2, NF-κB and Snail was observed in the gastric cancer tissues, whereas there was a considerable reduction in E-cadherin expression in the cancer tissues compared to the normal gastric mucosa. The expression patterns of COX-2, NF-κB and Snail were similar. The increased expression of COX-2 in the gastric cancer tissues closely correlated with the increased expression of NF-κB and Snail, but inversely correlated with the expression of E-cadherin. Treatment of the SGC7901 cells (which express high levels of COX-2) with celecoxib, a COX-2 inhibitor, not only led to a marked dose- and time-dependent decrease in the expression of COX-2, NF-κB and Snail, but also led to a significant increase in the expression of E-cadherin, and this was associated with a reduction in cell invasion. By contrast, the same treatment did not alter the expression of these genes in another gastric cancer cell line, MGC803 (which barely expresses COX-2). These data suggest that COX-2 regulates the expression of E-cadherin through the NF-κB and Snail signaling pathway in gastric cancer.
authors.affiliation: Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Zenan
authors.initials: Z
authors.lastname: Hu
authors.forename: Yongning
authors.initials: Y
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt