Korean J Otorhinolaryngol-Head Neck Surg.  2010 Jul;53(7):430-435. 10.3342/kjorl-hns.2010.53.7.430.

Enhanced Effect of Combinatorial Inhibition of Cyclooxygenase-2 and 5-Lipoxygenase on Head and Neck Cancer Cells

• Park SW
• Sung MW

• KMID: 2037230
• DOI: http://doi.org/10.3342/kjorl-hns.2010.53.7.430

Abstract

BACKGROUND AND OBJECTIVES
It has recently been found that arachidonate 5-lipoxygenase (5-lipoxygenase, 5-LO or ALOX5), another molecule capable of arachidonic acid (AA) metabolism, might promote cancer cell viability through unique mechanisms. Interestingly, 5-LO appears to have similar mechanisms to prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2, COX-2) in the regulation of cell viability, although it often utilizes different signaling pathways. We found that not only COX-2 expression but also the expression of 5-LO is up-regulated in some of head and neck squamous cell carcinoma (HNSCC) cell lines. From these findings, we hypothesized that the combined inhibition of these pathways would be likely to be a more effective anti-cancer modality with less side-effect in HNSCC. MATERIALS AND METHOD: In HNSCC cell lines, we investigated the expression of COX-2 and 5-LO by western blotting and checked the levels of prostaglandin E2, leukotrien B4 and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay. We performed MTT assay to analyze the growth-inhibitory effect of COX-2 and 5-LO inhibition.
RESULTS
Actually, combined knock-down of COX-2 and 5-LO resulted in an enhanced inhibitory effect in cell proliferation of HNSCC than a single inhibition of COX-2. Furthermore, we observed that VEGF production was blocked more effectively by combined treatment of COX-2 and 5-LO small interfering RNA (siRNA) in all tested cell lines.
CONCLUSION
Therefore, the combined inhibition of COX-2 and 5-LO may be one way to overcome low efficacy of single inhibition of COX-2 in cancer cells with both COX-2 and 5-LO overexpression.

Keyword

Cyclooxygenase-2; COX-2; 5-Lipoxygenase; 5-LO; Head and neck cancer

MeSH Terms

Arachidonate 5-Lipoxygenase
Arachidonic Acid
Blotting, Western
Carcinoma, Squamous Cell
Cell Line
Cell Proliferation
Cell Survival
Cyclooxygenase 2
Dinoprostone
Enzyme-Linked Immunosorbent Assay
Head
Head and Neck Neoplasms
Neck
Prostaglandin-Endoperoxide Synthases
RNA, Small Interfering
Vascular Endothelial Growth Factor A
Arachidonate 5-Lipoxygenase
Arachidonic Acid
Cyclooxygenase 2
Dinoprostone
Prostaglandin-Endoperoxide Synthases
RNA, Small Interfering
Vascular Endothelial Growth Factor A