Abstract
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 COX‐1 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. © 2010 Wiley Periodicals, Inc. Head Neck, 2010