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KMID : 0371320010600010047
Journal of the Korean Surgical Society
2001 Volume.60 No. 1 p.47 ~ p.54
Study in the Relationship between Angiogenic Factor and Expression of Cyclooxygenase and Nitric Oxide Synthase in Gastric Cancer
Lee Ik-Ryong

Kim Won-Jin
Kim Min-Chan
Jung Ghap-Joong
Choi Hong-Jo
Kwak Jong-Young
Joh Se-Heon
Kim Young-Hoon
Kim Hyung-Ho
Kim Sang-Sun
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
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