Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression
Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression
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DOI：
10.1046/j.1538-7836.2003.00446.x
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发表时间：
2003-10-01
影响因子：
10.4
通讯作者：
Wu, KK
中科院分区：
文献类型：
--
作者：
Shtivelband, MI;Juneja, HS;Wu, KK
为了确定阿司匹林和水杨酸盐是否抑制结肠癌细胞介导的血管生成，我们评估了阿司匹林和水杨酸钠对基质胶上内皮管形成的影响。阿司匹林和水杨酸钠浓度依赖性地抑制由从DLD-1收集的条件培养基诱导的人内皮细胞（EC）管形成。HT-29或HCT-116结肠癌细胞。阿司匹林和水杨酸钠在药理学浓度下同样有效地阻断管形成。中和抗血管内皮生长因子（VEGF）抗体阻断结肠癌培养基诱导的管形成。VEGF受体2而不是受体I抗体抑制管形成的程度与抗VEGF抗体相似。这些结果表明，VEGF与VEGF受体2的相互作用是结肠癌诱导血管生成的主要机制。阿司匹林或水杨酸钠以浓度依赖性方式抑制VEGF诱导的管形成，与抑制结肠癌培养基诱导的内皮管形成的方式相当。研究表明，环氧合酶-2（考克斯-2）在肿瘤血管生成中起关键作用。我们发现，结肠癌介质诱导的考克斯-2蛋白在EC中的表达和阿司匹林或水杨酸钠抑制癌症诱导的考克斯-2蛋白水平，其浓度与抑制内皮管形成的浓度相关。阿司匹林和水杨酸钠可抑制VEGF刺激的考克斯-2表达。这些发现表明，阿司匹林和其他水杨酸类药物在药理学浓度下抑制结肠癌诱导的血管生成，这与考克斯-2抑制相关。
To determine whether aspirin and salicylate suppress colon cancer cell-mediated angiogenesis, we evaluated the effects of aspirin and sodium salicylate on endothelial tube formation on Matrigel. Aspirin and sodium salicylate concentration-dependently inhibited human endothelial cell (EC) tube formation induced by conditioned medium collected from DLD-1. HT-29 or HCT-116 colon cancer cells. Aspirin and sodium salicylate at pharmacological concentrations were equally effective in blocking tube formation. Neutralizing antivascular endothelial growth factor (VEGF) antibodies blocked colon cancer medium-induced tube formation. VEGF receptor 2 but not receptor I antibodies inhibited tube formation to a similar extent as anti-VEGF antibodies. These results indicate that VEGF interaction with VEGF receptor 2 is the primary mechanism underlying colon cancer-induced angiogenesis. Aspirin or sodium salicylate inhibited VEGF-induced tube formation in a concentration-dependent manner comparable to that of inhibition of colon cancer medium-induced endothelial tube formation. It has been shown that cyclooxygenase-2 (COX-2) is pivotal in cancer angiogenesis. We found that colon cancer medium-induced COX-2 protein expression in EC and aspirin or sodium salicylate suppressed the cancer-induced COX-2 protein levels at concentrations correlated with those that suppressed endothelial tube formation. Furthermore, aspirin and sodium salicylate inhibited COX-2 expression stimulated by VEGF. These findings indicate that aspirin and other salicylate drugs at pharmacological concentrations inhibit colon cancer-induced angiogenesis which is correlated with COX-2 suppression.