J Korean Surg Soc.  2001 Jan;60(1):47-54.

Study in the Relationship between Angiogenic Factor and Expression of Cyclooxygenase and Nitric Oxide Synthase in Gastric Cancer

• Lee IR
• Kim MC
• Kim HH
• Choi HJ
• Kim YH
• Cho SH
• Jung GJ
• Kim SS
• Kim WJ
• Kwak JY

Abstract

PURPOSE: Secretion of angiogenic factors from tumor cells is know to play an important role in neo-vascularization and metastasis. However, which angiogenic factor is related with the formation of neo-vasculature in gastric carcinomas is not well known. This study was performed to observe changes in the expression of vascular endothelial growth factor (VEGF), cyclooxygenase (COX), and nitric- oxide synthase (NOS).
METHODS
Expressions of VEGF, COX, and NOS in thirty specimens resected from patients with a gastric carcinoma were investigated using the western blot method. Cultured MKN28 gastric cancer cells were treated with 100 ng/ml VEGF, and changes in the expression of COX and NOS were examined. Changes in VEGF expression were also investigated after treatment of the cells with inhibitors of COX and NOS.
RESULTS
Expressions of VEGF, COX, and eNOS were increased up to 10, 60, and 30%, respectively, in tumors compared to surrounding normal tissues. VEGF-positive tumors showed a higher expression of COX-2. Human recombinant VEGF induced the expression of COX-2, but not eNOS, in the cultured MKN28 cells. The increase in expression was blocked with actinomycin D, the VEGF antibody, and anti-VEGF peptide. VEGF-induced expression of COX-2 was also blocked by pretreatment of cells with aspirin and indomethacin, suggesting that these anti-inflammatory drugs inhibit VEGF. The expression of eNOS was decreased by indomethacin in VEGF-treated cells, but COX-2 expression was not affected by inhibitors of NO production, N-arginine methylester (NAME). However, the protein level of VEGF was increased by indomethacin and NAME.
CONCLUSION
This study showed that COX-2 and eNOS in gastric carcinomas seem to play an important role in the production of VEGF and that their expressions may also be affected by VEGF.

Keyword

Gastric cancer; Angiogenesis; Cyclooxygenase; Vascular endothelial growth factor; Nitric oxide synthase

MeSH Terms

Angiogenesis Inducing Agents*
Aspirin
Blotting, Western
Dactinomycin
Humans
Indomethacin
Neoplasm Metastasis
Nitric Oxide Synthase*
Nitric Oxide*
Prostaglandin-Endoperoxide Synthases*
Stomach Neoplasms*
Vascular Endothelial Growth Factor A
Angiogenesis Inducing Agents
Aspirin
Dactinomycin
Indomethacin
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Vascular Endothelial Growth Factor A