Leung Wai K, To Ka F, Go Minnie Y Y, Chan Ka-Kui, Chan Francis K L, Ng Enders K W, Chung S C Sydney, Sung Joseph J Y
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
Int J Oncol. 2003 Nov;23(5):1317-22.
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.
尽管环氧合酶（COX）-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COX-2表达与胃癌细胞及人类胃癌中血管内皮生长因子（VEGF）表达之间的关联。用表达cox-2的载体瞬时转染胃细胞系Kato III。转染后测量COX-2、前列腺素（PG）E2和VEGF的表达水平。此外，通过对存档胃切除标本进行免疫组织化学检测，确定人类胃癌中COX-2和VEGF的表达。通过微血管密度（MVD）评估肿瘤血管生成，MVD通过抗CD34免疫染色确定。用cox-2瞬时转染Kato III与COX-2表达增加、PGE2产生增加和VEGF表达上调有关。用特异性COX-2抑制剂NS398处理可使表达COX-2的Kato III细胞中的VEGF表达降低25%。在检测的67例胃癌中，45例（67%）存在COX-2过表达，而46例（69%）检测到VEGF表达增加。胃癌中COX-2和VEGF表达之间存在显著关联（r=0.25，p=0.041）。此外，肿瘤MVD与COX-2（r=0.32，p=0.008）和VEGF（r=0.39，p=0.001）表达均相关。我们的结果表明，胃细胞和原发性胃癌中COX-2的过表达与VEGF上调和血管生成有关。未来的研究应评估COX-2抑制剂对人类胃癌的潜在抗血管生成作用。
