Effects of cyclooxygenase 2 inhibitors on biological traits of nasopharyngeal carcinoma cells.
OBJECTIVE
To investigate effects of cyclooxygenase 2 (COX-2) inhibitors on nasopharyngeal carcinoma (NPC) cells and on angiogenesis in vitro.


METHODS
Human NPC cell lines (CNE1, CNE2 and SUNE) were treated with nimesulide or celecoxib. MTT assay and colony formation assay were performed to observe antiproliferation activity of COX-2 inhibitors to NPC cell lines. Cell cycle arrest and apoptosis of NPC cell strains were tested by flow cytometry assay, microscopic morphology observation, and DNA fragmentation assay. The effect of COX-2 inhibitor on angiogenesis was tested by chick chorioallantoic membrane (CAM) model.


RESULTS
Nimesulide (Nim) and celecoxib (Cel) could antiproliferate NPC cell lines with IC50 182 micromol/L(Nim-SUNE), 78 micromol/L(Nim-CNE1), 175 micromol/L(Nim-CNE2), 7.2 micromol/L(Cel-SUNE), 8.1 micromol/L(Cel-CNE1), and 7.6 micromol/L(Cel-CNE2). The antiproliferation presented dose-dependent (Nim 5-400 micromol/L, Cel 0.5-80 micromol/L) and time-dependent manner (Nim IC50 562 micromol/L(24 h), 316 micromol/L(48 h), 50.1 micromol/L(240 h)). Nim and Cel arrested SUNE and CNE1 cell cycle at phase G2/M (cell aggregation rate 28.9%-45.1%(Nim 25-200 micromol-12 h-SUNE), 18.9%-26.2%(Nim 25-200 micromol-24 h-SUNE), 28.8%-35.6%(Nim 25-200 micromol-48 h-SUNE), 30.4%-16.4%(Cel 25-100 micromol-12 h-SUNE), 21.2%-19.7%(Cel 25-100 micromol-24 h-SUNE), 31.1%-19.9%(Cel 25-100 micromol-24 h-SUNE), 20.5%-34.1%(Nim25-200 micromol-12 h-CNE1), 25.2%-26.9%(Nim 25-200 micromol-24 h-CNE1), 11.5%-7.1% (Nim 25-200 micromol-48 h-CNE1)). Apoptosis shape and apoptosis strap displayed in NPC cells after treatment with Nim and Cel. Nim had a feature of anti-angiogenesis on CAM model.


CONCLUSIONS
Nim and Cel could suppress proliferation of squamous epithelium NPC cell (SUNE, CNE1 and CNE2) through blocking cell cycle and inducing cell apoptosis. Nim could apparently suppress CAM angiogenesis induced by SUNE cell.
Chen
Pei-yi
PY
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China. peiyichen@163.net
Long
Qi-cai
QC
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology; D008565:Membrane Proteins; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; C012655:nimesulide