Correlation between nitric oxide and cyclooxygenase-2 pathways in head and neck squamous cell carcinomas

被引:38
作者
Gallo, O
Fabbroni, V
Sardi, I
Magnelli, L
Boddi, V
Franchi, A
机构
[1] Univ Florence, Sch Med, Dept Human Pathol & Oncol, I-50134 Florence, Italy
[2] Univ Florence, Sch Med, Dept Otoneuroophthalmol Surg, I-50134 Florence, Italy
[3] Univ Florence, Sch Med, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy
[4] Univ Florence, Sch Med, Med Genet Unit, Dept Clin Physiopathol, I-50139 Florence, Italy
关键词
head and neck cancer; inducible nitric oxide; cyclooxygenase-2; angiogenesis;
D O I
10.1016/S0006-291X(02)02683-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:517 / 524
页数:8
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