DIFFERENTIAL EFFECTS BETWEEN CYCLOOXYGENASE-2 INHIBITORS AND siRNA ON VASCULAR ENDOTHELIAL GROWTH FACTOR PRODUCTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

DIFFERENTIAL EFFECTS BETWEEN CYCLOOXYGENASE-2 INHIBITORS AND siRNA ON VASCULAR ENDOTHELIAL GROWTH FACTOR PRODUCTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

DIFFERENTIAL EFFECTS BETWEEN CYCLOOXYGENASE-2 INHIBITORS AND siRNA ON VASCULAR ENDOTHELIAL GROWTH FACTOR PRODUCTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

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. VC 2010 Wiley Periodicals, Inc. Head Neck 32:1534–1543, 2010
Keywords: cyclooxygenase-2; COX-2; COX-1; VEGF; small interfering RNA

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