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 COX-1 and COX-2 in tested cells.


CONCLUSIONS
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.
Park
Seok-Woo
SW
Cancer Research Institute, Seoul National University College of Medicine, 28, Yongun-dong, Chongno-gu, Seoul, Korea.
Kim
Hyo-Sun
HS
Hah
Jeong-Hun
JH
Kim
Kwang-Hyun
KH
Heo
Dae-Seog
DS
Sung
Myung-Whun
MW
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D034741:RNA, Small Interfering / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone