위암에서 Cyclooxygenase와 Nitric Oxide Synthase 발현과 혈관신생인자와의 관계에 대한 연구
Study in the Relationship between Angiogenic Factor and Expression of Cyclooxygenase and Nitric Oxide Synthase in Gastric Cancer
이익룡, 김원진, 김민찬, 정갑중, 최홍조, 곽종영, 조세헌, 김영훈, 김형호, 김상순,
소속 상세정보
이익룡 ( Lee Ik-Ryong )
동아대학교 의과대학 외과학교실
김원진 ( Kim Won-Jin )
동아대학교 의과대학 생화학교실
김민찬 ( Kim Min-Chan )
동아대학교 의과대학 외과학교실
정갑중 ( Jung Ghap-Joong )
동아대학교 의과대학 외과학교실
최홍조 ( Choi Hong-Jo )
동아대학교 의과대학 외과학교실
곽종영 ( Kwak Jong-Young )
동아대학교 의과대학 생화학교실
조세헌 ( Joh Se-Heon )
동아대학교 의과대학 외과학교실
김영훈 ( Kim Young-Hoon )
동아대학교 의과대학 외과학교실
김형호 ( Kim Hyung-Ho )
동아대학교 의과대학 외과학교실
김상순 ( Kim Sang-Sun )
동아대학교 의과대학 외과학교실
KMID : 0371320010600010047
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.
키워드
위암;혈관신생;사이크로옥시제나아제;혈관내피세포성장인자;아산화질소 합성효소
Gastric cancer;Angiogenesis;Cyclooxygenase;Vascular endothelial growth factor;Nitric oxide synthase
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