Correlation between nitric oxide and cyclooxygenase-2 pathways in head and neck squamous cell carcinomas.
We investigated the interactions between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) pathways in head and neck squamous cell carcinomas (HNSCCs) and in two carcinoma cell lines. HNSCCs showed an up-regulation of both pathways which were strongly correlated with each other (p=0.02) and with tumor vascularization (p=0.0001 and p=0.008, respectively). In carcinoma cells, Escherichia coli lipopolysaccharide (LPS) and EGF treatment up-regulated both pathways. NOS inhibitor N(G)-monomethyl-L-arginine methyl ester (L-NAME) inhibited this up-regulation. LPS or EGF induced iNOS expression that was not altered by NOS or COX-2 inhibitors. Conversely, LPS or EGF promoted COX-2 expression that was decreased by L-NAME. The NO donor S-nitroso-acetyl-penicillamine (SNAP) up-regulated COX-2 pathway and this effect was reduced by the guanylate cyclase inhibitor methylene blue. Thus, in squamous carcinoma cells, NO increases the activity of COX-2 pathway and this effect is probably mediated by endocellular cGMP level, with potential implications on tumor growth, angiogenesis, and therapy.
Gallo
Oreste
O
Department of Oto-Neuro-Ophthalmologic Surgery, University of Florence Medical School, 50134 Florence, Italy.
Fabbroni
Valentina
V
Sardi
Iacopo
I
Magnelli
Lucia
L
Boddi
Vieri
V
Franchi
Alessandro
A
D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D006152:Cyclic GMP / Q000378:metabolism; D051546:Cyclooxygenase 2; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013223:Statistics as Topic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D026423:S-Nitroso-N-Acetylpenicillamine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP