Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition.
Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition.
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姜黄素通过COX-2和MAPK抑制作用抑制人肠微血管内皮细胞中VEGF介导的血管生成。
DOI：
10.1136/gut.2008.152496
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发表时间：
2008-11
期刊：
影响因子：
24.5
通讯作者：
Rafiee, P.
中科院分区：
文献类型：
--
作者：
Binion, D. G.;Otterson, M. F.;Rafiee, P.
血管生成，即新血管的生长，是一种重要的稳态机制，其响应生理要求和病理生理需求（包括慢性炎症和癌症）来调节血管群。血管生成在胃肠道慢性炎症和癌症中的重要性已经被定义，因为抗血管生成治疗已经在炎症性肠病和结肠癌治疗模型中证明了益处。姜黄素是一种天然产物，正在接受慢性炎症治疗的评估，包括炎症性肠病（IBD）。姜黄素对人肠血管生成的影响尚未确定。姜黄素对体外血管生成的抗血管生成作用进行了研究，使用原代培养的人肠微血管内皮细胞（HIMECs），血管内皮生长因子（VEGF）刺激。姜黄素抑制VEGF诱导的HIMECs增殖、细胞迁移和管腔形成。VEGF激活HIMECs可导致环氧合酶-2（考克斯-2）mRNA、蛋白表达和前列腺素E2（PGE 2）的产生增加。用10 μM姜黄素和1 μM选择性考克斯-2抑制剂NS 398预处理HIMECs，可在mRNA和蛋白水平抑制考克斯-2，并抑制PGE 2的产生。类似地，考克斯-2在HIMECs中的表达被Jun N-末端激酶（JNK; SP 600125）和p38丝裂原活化蛋白激酶（MAPK; SB 203580）抑制剂显著抑制，并且被p44/42 MAPK抑制剂（PD 098059）降低。总之，这些数据表明考克斯-2在通过MAPK调节HIMEC中的血管生成中具有重要作用。此外，姜黄素通过抑制考克斯-2表达和PGE 2产生来抑制微血管内皮细胞血管生成，表明这种天然产物具有抗血管生成特性，这值得进一步研究作为IBD和癌症的辅助治疗。
Angiogenesis, the growth of new blood vessels, is a critical homeostatic mechanism which regulates vascular populations in response to physiological requirements and pathophysiological demand, including chronic inflammation and cancer. The importance of angiogenesis in gastrointestinal chronic inflammation and cancer has been defined, as antiangiogenic therapy has demonstrated benefit in models of inflammatory bowel disease and colon cancer treatment. Curcumin is a natural product undergoing evaluation for the treatment of chronic inflammation, including inflammatory bowel disease (IBD). The effect of curcumin on human intestinal angiogenesis is not defined. The antiangiogenic effect of curcumin on in vitro angiogenesis was examined using primary cultures of human intestinal microvascular endothelial cells (HIMECs), stimulated with vascular endothelial growth factor (VEGF). Curcumin inhibited proliferation, cell migration and tube formation in HIMECs induced by VEGF. Activation of HIMECs by VEGF resulted in enhanced expression of cyclo-oxygenase-2 (COX-2) mRNA, protein and prostaglandin E2 (PGE2) production. Pretreatment of HIMECs with 10 μM curcumin as well as 1 μM NS398, a selective inhibitor of COX-2, resulted in inhibition of COX-2 at the mRNA and protein level and PGE2 production. Similarly COX-2 expression in HIMECs was significantly inhibited by Jun N-terminal kinase (JNK; SP600125) and p38 mitogen-activated protein kinase (MAPK; SB203580) inhibitors and was reduced by p44/42 MAPK inhibitor (PD098059). Taken together, these data demonstrate an important role for COX-2 in the regulation of angiogenesis in HIMECs via MAPKs. Moreover, curcumin inhibits microvascular endothelial cell angiogenesis through inhibition of COX-2 expression and PGE2 production, suggesting that this natural product possesses antiangiogenic properties, which warrants further investigation as adjuvant treatment of IBD and cancer.
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