Abstract
High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC). Five human OPC cell lines tested expressed both isoforms of cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and significantly decreased PGE2 production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1α, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes transduction to occur via STAT3 pathway activation. Coincubation with OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth proportional to the IL-6 levels measured in the conditioned medium. This growth effect was specifically inhibited by anti-IL-6 antibody. These results are consistent with cytokine products of inflammatory cells having paracrine growth effects on OPC. If chronic inflammation plays a role in promoting the development of OPC, this mechanism may also apply to other epithelial tumor systems modulated by COX activity.
Original language | English (US) |
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Pages (from-to) | 1499-1507 |
Number of pages | 9 |
Journal | FASEB Journal |
Volume | 14 |
Issue number | 11 |
DOIs | |
State | Published - 2000 |
Keywords
- Arachidonic acid
- COX inhibitors
- Colon cancer
- Inflammatory disease