摘要
目的研究环氧合酶(cyclooxygenase,COX)非选择性抑制剂布洛芬和COX-2选择性抑制剂氮-2,环己氧-4,硝基苯-甲级磺胺(NS398)对卵巢肿瘤血管形成的影响,并探讨其作用机制。方法2007年于北京协和医院,通过体外细胞共培养模型,观察COX抑制剂对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)迁移能力的影响。采用逆转录聚合酶链反应(RT-PCR)检测COX抑制剂对OVCAR3血管内皮生长因子(vascularendothelial growth factor,VEGF)mRNA表达的影响。采用ELISA方法检测COX抑制剂对OVCAR3中VEGF和前列腺素E2(prostaglandin E2,PGE2)分泌的影响。结果两种COX抑制剂都能抑制HUVEC的迁移,抑制OVCAR3细胞中VEGF mRNA的表达和VEGF、PGE2的分泌。经NS398处理后,研究组HUVEC迁移细胞数目明显低于对照组[(39.0±3.8)个/400×视野vs(56.0±4.2)个/400×视野,P<0.05]。结论NS398和布洛芬通过抑制PGE2,在mRNA和蛋白水平下调VEGF的合成分泌,抑制血管内皮细胞的迁移。COX抑制剂可能成为干预卵巢肿瘤血管形成的一个新选择。
Objective To investigate the effect and mechanism of non COX - selective inhibitor - ibuprofen and COX - 2 selective inhibitor - NS398 on the angiogenesis in ovarian carcinoma. Methods Cell co - culture model was established to observe the COX inhibitors＂ effect on the motility of endothelial cells. The expression of VEGF mRNA was determined by RT - PCR after the treatment of COX inhibitors. Production of VEGF and PGE2 was determined by ELISA. Results Both COX non - selevtive inhibitor and COX - 2 selective inhibitor were all observed to reduce the motility of endothelial cells through the matrigel in the co - culture model. The mobility cells of HUVEC were reduced significantly when cocultured with OVCAR3 that treated by ibuprofen （42. 0 ± 3.2/400× field vs 56.0 ± 4.2/400 × field, P 〈0. 05 ）, The mobility cells of HUVEC were reduced significantly when cocuhured with OVCAR3 that treated by NS598 （ 39. 0 ±3.8/400 × field vs 56. 0 ± 4. 2/400 × field, P 〈 0. 05 ）. The expression of VEGF mRNA was down - regulated by both ibuprofen and NS398 in OVCAR3. The Production of VEGF and PGE2 in the cell culture supernatant were less than control group after the treatment of COX inhibitors. Conclusion The anti - angiogenesis effect of COX inhibitors was observed through down - regulating the expression of VEGF mRNA and decreasing the protein secretion of VEGF. The COX inhibitors＇effect on VEGF was proposed through the PGs pathway. Ibuprofen and NS398 maybe become a new strategy in the chemoprevention and treatment of epithelial ovarian carcinoma in the near future.
出处
《中国实用妇科与产科杂志》
CAS
CSCD
北大核心
2009年第6期438-440,共3页
Chinese Journal of Practical Gynecology and Obstetrics
基金
国家自然科学基金(30240063)
关键词
卵巢肿瘤
环氧合酶抑制剂
血管形成
细胞共培养
ovarian neoplasms
cyclooxygenase inhibitor
angiogenesis
cell co - culture
