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

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.