环氧合酶-2调控血管内皮生长因子表达的研究

目的 环氧合酶-2参与肿瘤的发生发展，但其在致癌过程中的作用机制尚不清楚。对胚胎小鼠成纤维细胞中不同基因型的环氧合酶(COX)，如COX-1^-/-/COX-2^-/-及野生型COX-1^ / ／COX-2^ / 与血管内皮生长因子(VEGF)表达的关系进行探讨。方法 培养小鼠胚胎成纤维细胞，用ELISA方法测量细胞中VEGF水平，从培养的细胞中提取mRNA，用RT-PCR技术确定VEGF的表达。结果 在COX-2基因缺失(COX-2^-/-)细胞中几乎测不出VEGF，而在含有COX-2基因(COX-2^ / )的细胞中VEGF水平明显增高，抑制剂赛来昔布(celecoxib)能抑制VEGF。VEGF的水平与COX-1无关。COX-2在mRNA水平调控VEGF的表达。结论 COX-2在VEGF的分泌与合成中起重要作用，从而影响肿瘤新生血管生成及肿瘤生长。

Effects of cyclooxygenase-2 on expression of vascular endothelial growth factor

Objective It has been known that cyclooxygenase-2(COX-2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in the processes of carcinogenesis remains unclear. The study was designed to observe the relationship between expression of COX and the expression of vascular endothelial growth factor (VEGF) in the mouse embryo fibroblast (MEF) with knock out of COX-1 gene (COX-1 -/- ) or COX-2 gene (COX-2 -/- ) and wild MEF cells (COX-1 +/+ /COX-2 +/+ ). Methods We cultured the mouse embryo fibroblasts, measured the VEGF levels in the culture medium of these cells using ELISA, and extracted mRNA from these cells to identify the expressions of VEGF isoforms by RT-PCR. Results VEGF level could hardly be measured in the COX 2-deficient cells (COX-2 -/- ), however, the VEGF level was significantly increased in the cells with COX-2 gene (COX-2 +/+ ) and decreased by celecoxib, a COX-2 inhibitor. The level of VEGF was not associated with COX-1 expression. COX-2 inhibited the expressions of three isoforms of VEGF at mRNA level. Conclusions COX-2 plays an important role in the VEGF secretion and synthesis and therefore, it has an effect on the angiogenesis and tumor growth.