Differential effects between cyclooxygenase-2 inhibitors and siRNA on vascular endothelial growth factor production in head and neck squamous cell carcinoma cell lines.

Background. Several researchers have observed that cyclooxygenase-2 (COX-2) inhibitors display anticancer effects only at higher concentrations than doses that block COX-2 activity in head and neck squamous cell carcinoma (HNSCC) cells. Methods. To better understand the exact anticancer mechanism of COX-2-inhibitors, we compared the effects of pharmacologic inhibitors to those of small-interfering RNA against COX-2 on cell-growth, vascular endothelial growth factor (VEGF) production, and intracellular signaling in HNSCC cell lines. Results. We observed in HNSCC cells, that COX-2-siRNA induced an inhibitory effect on intracellular signaling, but unlike the pharmacologic inhibitors, did not affect cell proliferation. Whereas the chemical inhibitors increased VEGF synthesis even at low doses, COX-2-siRNA showed differential inhibition of VEGF production according to expression patterns of COX1 and COX-2 in tested cells. Conclusion. The majority of the anticancer effects of COX-2-inhibitors in HNSCC cells seem to result from COX-2-independent action, suggesting that COX-1 and COX-2 may contribute to VEGF synthesis in cancer cells through a prostaglandin-dependent mechanism. (C) 2010 Wiley Periodicals, Inc. Head Neck 32: 1534-1543,2010