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: 1534-1543,2010Park JW, 2006, J CANCER RES CLIN, V132, P184, DOI 10.1007/s00432-005-0060-xCharames GS, 2006, INT J ONCOL, V28, P543Palayoor ST, 2005, CLIN CANCER RES, V11, P6980, DOI 10.1158/1078-0432.CCR-05-0326Kino Y, 2005, PROSTAG LEUKOTR ESS, V73, P103, DOI 10.1016/j.plefa.2005.04.014Zhi YH, 2005, WORLD J GASTROENTERO, V11, P3724Maier TJ, 2005, FASEB J, V19, P1353, DOI 10.1096/fj.04-3274fjeDaikoku T, 2005, CANCER RES, V65, P3735Brown JR, 2005, J CLIN ONCOL, V23, P2840Honjo S, 2005, DNA CELL BIOL, V24, P141Wang Z, 2005, CURR PHARM DESIGN, V11, P1771Farivar-Mohseni H, 2004, AM J SURG, V188, P505, DOI 10.1016/j.amjsurg.2004.07.025Roh JL, 2004, CANCER RES, V64, P3230Maier TJ, 2004, BIOCHEM PHARMACOL, V67, P1469, DOI 10.1016/j.bcp.2003.12.014Shao JY, 2004, J BIOL CHEM, V279, P14287, DOI 10.1074/jbc.M313276200Kinugasa Y, 2004, CLIN EXP METASTAS, V21, P737, DOI 10.1007/s10585-005-1190-xPark SW, 2003, INT J CANCER, V107, P729, DOI 10.1002/ijc.11498Regan JW, 2003, LIFE SCI, V74, P143, DOI 10.1016/j.lfs.2003.09.031Denkert C, 2003, ONCOGENE, V22, P8653, DOI 10.1038/sj.onc.1206920Shao JY, 2003, CANCER RES, V63, P5218Soh JW, 2003, PROG EXP TUMOR RES, V37, P261Muller-Decker K, 2002, P NATL ACAD SCI USA, V99, P12483, DOI 10.1073/pnas.192323799Lee DW, 2002, ANTICANCER RES, V22, P2089Baek SJ, 2002, J PHARMACOL EXP THER, V301, P1126Elder DJE, 2002, INT J CANCER, V99, P323, DOI 10.1002/ijc.10330Sheng HM, 2001, J BIOL CHEM, V276, P18075Warner TD, 1999, P NATL ACAD SCI USA, V96, P7563EBERHART CE, 1994, GASTROENTEROLOGY, V107, P1183