The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture.
Angiogenesis, the development of new blood vessels from preexisting capillaries, is essential for the development, growth and advancement of solid tumours. Angiogenesis is enhanced by prostaglandins (PGs) that are synthesised by the catalysis of cyclooxygenases (COX-1 and COX-2) from arachidonic acid. COX-2 is upregulated in a variety of malignancies and favours the growth of malignant cells by stimulating proliferation and angiogenesis. The aim of this study is to investigate the angiogenetic process by determining the levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 in endometrial cancer cells and to study the effect of nimesulide, a selective COX-2 inhibitor, on these mediators using cell culture. Endometrial tissue specimens were obtained from subjects with endometrial cancer and intramural leiomyoma. Cells were incubated with either 10 or 50 microM nimesulide for 24 h. VEGF, MCP-1 and IL-8 concentrations were determined by sandwich quantitative enzyme immunoassay (ELISA). VEGF concentration was significantly higher in cancer cells than normal endometrial cells. VEGF was decreased with 10 microM nimesulide in cancer cells whereas it remained unaltered in normal cells. Both MCP-1 and IL-8 concentrations were lower in cancer cells than normal cells. MCP-1 levels were decreased with both doses of nimesulide in normal cells, whereas IL-8 levels were significantly affected only by 50 microM of nimesulide. These results suggest that COX-2 inhibitors may be effective in the treatment of endometrial cancer via suppression of angiogenesis.
Genç
S
S
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa 34093, Istanbul, Turkey. semgenc@hotmail.com
Attar
E
E
Gürdöl
F
F
Kendigelen
S
S
Bilir
A
A
Serdaroğlu
H
H
D018932:Chemokine CCL2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016861:Cyclooxygenase Inhibitors; D016209:Interleukin-8; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C012655:nimesulide