Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production.
Prostaglandins (PGs) are known to play important roles in the proliferation of various types of cancer cells. PGs are produced by the action of cyclooxygenase (COX) enzymes, and two forms of COX, COX-1 and COX-2, have been described. Previous studies have demonstrated that overexpression of COX-2 is associated with colon carcinogenesis, tumor invasion and metastatic potential of colon cancer. In this study, the role of COX-2 on proliferation of squamous cell carcinoma cell lines was investigated. NS-398, a selective COX-2 inhibitor, inhibited proliferation of NA cells, a squamous cell caricinoma cell line that constitutively expresses COX-2 mRNA. NS-398 suppressed the spontaneous production of PGE2 by NA cells, and the antiproliferative effect of NS-398 was abolished by addition of PGE2. Similar results were obtained from experiments using COX-2 antisense oligonucleotide. These results suggest that specific inhibition of COX-2 inhibits proliferation of cancer cells expressing COX-2 mRNA via suppression of PGE2 production.
Sumitani
K
K
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
Kamijo
R
R
Toyoshima
T
T
Nakanishi
Y
Y
Takizawa
K
K
Hatori
M
M
Nagumo
M
M
D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014062:Tongue Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone