Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma.
Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma.
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DOI：
10.3892/ijo.23.5.1317
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发表时间：
2003-11
影响因子：
5.2
通讯作者：
W. Leung;K. To;M. Go;Ka-Kui Chan;F. Chan;E. Ng;S. Chung;J. Sung
中科院分区：
文献类型：
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作者：
W. Leung;K. To;M. Go;Ka-Kui Chan;F. Chan;E. Ng;S. Chung;J. Sung
尽管环氧合酶（考克斯）-2过表达的胃癌与预后不良相关，但其机制途径仍不清楚。我们研究了胃癌细胞和人胃癌中考克斯-2和血管内皮生长因子（VEGF）的表达之间的关系。用考克斯-2表达载体瞬时转染胃细胞系Kato III。转染后检测考克斯-2、前列腺素（PG）E2和VEGF的表达水平。同时采用免疫组化法检测胃癌组织中考克斯-2和VEGF的表达。采用抗CD 34免疫组化法检测肿瘤微血管密度（MVD），评价肿瘤血管生成。用COX-2瞬时转染Kato III与增加的考克斯-2表达、更高的PGE 2产生和上调的VEGF表达相关。用特异性考克斯-2抑制剂NS 398处理，使表达考克斯-2的Kato III细胞中VEGF表达降低25%。在67例胃癌中，45例（67%）发现考克斯-2过表达，46例（69%）检测到VEGF表达增加。胃癌组织中考克斯-2和VEGF的表达存在显著相关性（r=0.25，p=0.041）。此外，肿瘤MVD与考克斯-2（r=0.32，p=0.008）和VEGF（r=0.39，p=0.001）的表达相关。我们的研究结果表明，考克斯-2在胃细胞和原发性胃癌中的过表达与VEGF和血管生成的上调有关。未来的研究应评估考克斯-2抑制剂对人胃癌的潜在抗血管生成作用。
Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.