Journal Article

Significance of COX-2 expression in human esophageal squamous cell carcinoma

Huiying Zhi, Lin Wang, Jian Zhang, Chuannong Zhou, Fang Ding, Aiping Luo, Min Wu, Qimin Zhan and Zhihua Liu

in Carcinogenesis

Volume 27, issue 6, pages 1214-1221
Published in print June 2006 | ISSN: 0143-3334
Published online December 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi304
Significance of COX-2 expression in human esophageal squamous cell carcinoma

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Cyclooxygenase-2 (COX-2) is well established to play an important role in the tumorigenesis of a variety of human cancers; however, the function of COX-2 in the development of esophageal squamous cell carcinoma (ESCC) remains less clear. Here, we determined, first, the pattern of COX-2 expression in normal esophageal mucosa, dysplasia, carcinoma in situ (CIS) and invasive SCC. Immunohistochemical analysis showed that, while COX-2 was weakly expressed, if at all, in normal squamous epithelium, strong COX-2 expression was detected as early as the stage of dysplasia and frequently in 20 of 26 (77%) CIS and 86 of 111 (77%) invasive SCC. Upregulation of COX-2 in ESCC was found to be significantly associated with tumor progression (R = 0.493, P < 0.01). Further, treatment of human ESCC cell lines (KYSE450 and KYSE510) with NS-398, a COX-2 specific chemical inhibitor, suppressed the production of prostaglandin E2 (PGE2) and induced cell growth inhibition, cell cycle arrest at the G1–S checkpoint, and the expression of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Finally, knockdown expression of COX-2 in KYSE450 cells by a specific COX-2 siRNA dramatically inhibited PGE2 production, cell growth and, more importantly, colony formation and tumorigenesis in nude mice. Together, this study suggested that COX-2 may be involved in an early stage of squamous cell carcinogenesis of the esophagus and has a non-redundant role in the regulation of cellular proliferation and tumorigenesis of esophageal epithelial cells.

Keywords: CIS, carcinoma in situ; DMSO, dimethyl sulfoxide; ESCC, esophageal squamous cell carcinoma; ELISA, enzyme linked immunosorbent assay; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; NSAIDs, non-steroidal anti-inflammatory drugs; NS-398, N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulfonamide; PG, prostaglandin; RNAi, RNA interference

Journal Article.  5719 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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