Cycloxygenase-2 (COX-2) is one of the two isoforms that catalyzes the formation of prostaglandins from arachidonic acid. COX-1 is constitutively active and involved in regulation of renal blood flow and maintenance of gastric mucosa. Recent studies of COX-2 have shown that overexpression in a variety of human malignancies correlates with higher stage, larger tumor size, presence of lymphatic metastasis, and risk of recurrence. Therefore, overexpression of COX-2 is shown to result in enhanced cell proliferation and angiogenesis, both of which contribute to an aggressive tumor phenotype. One possible mechanism by which COX-2 acts is through activation of the immunoregulatory cytokine interleukin (IL-6) signaling pathway, which subsequently activates STAT3 (Signal transducer and activator of transcription). Persistent activation of STAT3, as phosphorylated STAT-3, is implicated in many human cancers by regulating genes that control cell proliferation, apoptosis, and angiogenesis. In our study, we hypothesized that HNSCC cell lines over-expressing COX-2 activate the IL-6/STAT3 pathway. COX-2 expression levels were measured using Western blot in 5 different HNSCC cell lines [CCL23, CAL27, SCC1, SCC12, SCC14A] and three primary tumors using COX-2 specific antibody. A lung cancer cell line (H2122) known to over-express COX-2 was used as a positive control. Phosphorylated (P-Ser727) STAT-3 expression levels were also measured using P-Ser727 STAT-3 specific antibody. Two cell lines, CAL27 and SCC1, appear to over-express COX-2. In CAL27, but not SCC1, COX-2 over-expression also correlated with elevated P-Ser727 STAT-3 levels. Though preliminary, these results indicate that COX-2 may be involved in activating the IL-6/STAT-3 pathway, and possibly other pathways such as the apoptotic pathway involving bcl-2.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.