中文摘要：

目的：探讨丹参酮ⅡA通过环氧化酶-2（COX-2）-Wnt/β-catenin信号通路调控人肠癌细胞血管内皮生长因子（VEGF）表达的作用机制。方法：分别采用PGE2和COX-2选择性抑制剂NS-398上调及抑制LoVo细胞COX-2表达,Western Blot检测COX-2对β-catenin蛋白表达的影响;分别采用丹参酮ⅡA、PGE2和/或GSK-3β选择性抑制剂SB-216763作用人肠癌HCT-116细胞24h,Western Blot法检测丹参酮ⅡA对COX-2和β-catenin蛋白表达的影响;ELISA法检测丹参酮ⅡA对VEGF表达的影响。结果：与对照组比较,PGE2能够显著上调LoVo细胞中COX-2蛋白表达,同时显著上调β-catenin在细胞总蛋白、浆蛋白和核蛋白中的表达水平;反之,COX-2抑制剂NS-398能够显著下调COX-2和β-catenin蛋白表达水平。丹参酮ⅡA能够显著下调COX-2和β-catenin蛋白在人肠癌LoVo细胞中表达水平,并且能够显著下调PGE2诱导的COX-2和β-catenin蛋白的高表达;同时,丹参酮ⅡA能够显著下调人肠癌LoVo细胞VEGF表达水平,并且能够下调PGE2和GSK-3β抑制剂SB-216763诱导的VEGF高表达。结论：丹参酮ⅡA通过抑制人肠癌细胞中COX-2的表达,阻止细胞中β-catenin的累积,从而阻断Wnt/β-catenin信号通路,下调VEGF表达,这可能是丹参酮ⅡA抗大肠癌血管新生的作用机制之一。

英文摘要：

Objective： To investigate the mechanism of Tanshinone ⅡA on VEGF expression via regulating COX-2-Wnt/β-catenin signaling pathway in colon cancer.Methods： Separately using PGE2 to up-regulate COX-2 and COX-2 selective inhibitor NS-398 to inhibit its expression in LoVo cells,the effect of COX-2 on β-catenin expression was detected by western blot;using TanshinoneⅡA,PGE2 and/or GSK-3β selective inhibitor SB-216763 in HCT-116 cells for 24h,the effect of Tanshinone ⅡA on COX-2 and β-catenin expression was detected by western blot;the effect of TanshinoneⅡA on VEGF expression was detected by ELISA.Results： PGE2 could increase COX-2 expression,also increase the level of β-catenin in the total cell,cytosolic and nuclear proteins compared with contrast group.COX-2 selective inhibitor NS-398 markedly decreased COX-2 expression,also decreased the level of β-catenin in the total cell,cytosolic and nuclear proteins.Tanshinone ⅡA reduced COX-2 and β-catenin protein expression in LoVo cells;TanshinoneⅡcould significantly decrease COX-2 and β-catenin protein expression,which were up-regulated by PGE2.TanshinoneⅡA decreased VEGF expression and induced-VEGF expression by PGE2 or GSK-3β selective inhibitor SB-216763.Conclusion： TanshinoneⅡA prevented accumulation of β-catenin,ultimately blocked Wnt/β-catenin signaling pathway and reduced VEGF expression by inhibiting COX-2 expressionⅡwhich was one of the possible mechanisms of TanshinoneⅡA on prevention and treatment of angiogenesis in colon cancer.