Effect Of COX-2 Expression Of Gastric Cancer Cells On Biological Behaviour Of Endothelial Cells

Cyclooxygenase (COX) is a key regulatory enzyme in the production of prostaglandin (PG) from arachidonic acid (AA). Accumulating evidence links COX-2, an enzyme already known to be involved in inflammation and cancer, with angiogenesis, suggesting that the studies of COX-2 signaling would aid the search for new molecular targets for the development of anti-angiogenic therapies. The current studies were planed to investigate whether the expression of COX-2 in gastric cancer cells can influence the proliferation, migration and tube-formation ability of endothelial cells (EC) in vitro. The main methods and results were the following:1. In SGC7901 and its derived two other gastric cancer cells, the COX-2 expression levels were detected by semi-quantitative RT-PCR and Western blotting methods. Antisense treatment for COX-2 gene significantly reduced the expression level of COX-2 protein and mRNA.2. The expression of endothelium-specific angiogenic factors was measured by semi-quantitative RT-PCR. Expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was reduced in gastric cancer cells after transfection with COX-2 antisense.3. Conditioned culture media from cells SGC7901. 7901-P and 7901-AS (COX-2 antisense transfected cells) were used to stimulate EC. and the proliferation, migrationand tube-formation ability of EC was assessed upon stimulation of the conditioned medium. When incubated with the conditioned medium from 7901-AS, proliferation, migration and tube-formation ability of EC was inhibited (P<0.05, P<0.01, P<0.01) compared to those from parental and empty-vector transfected cells.4. The tumor graft of 7901 -AS-cell in nude mice had less (P<0.05) vessel formation with microvessel density (MVD) 6.8?.8 compared to SGC7901 group MVD 9.4?.1 and 7901 -P group MVD 9.7?.8.All these results indicated that suppression of COX-2 in cancer cells reduces the angiogenesis by EC. The over expression of COX-2 may influence the proliferation, migration and angiogenesis of EC by altering the level of angiogenic factors in gastric cancer cells, and promote tumorgenesis, progression and metastasis of the tumor.