【作者】 任建琳； 刘宣； 陈文婷； 李琦；

【机构】 上海中医药大学附属市中医医院肿瘤科； 上海中医药大学附属普陀医院肿瘤科； 上海中医药大学中西医结合肿瘤介入研究所； 上海中医药大学附属曙光医院肿瘤科；

【摘要】 目的:探讨丹参酮ⅡA通过COX-2/PGE₂-β-catenin信号通路抑制人肠癌细胞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GSK-3β/β-catenin通路,下调VEGF表达,这可能是丹参酮H A抗大肠癌血管新生的作用机制之一。更多还原

【Abstract】 Objective:To investigate the mechanism of Tanshinone ⅡA on VEGF expression via regulating COX-2/PGE₂-B-catenin signal pathway in colon cancer.Methods:using PGE₂ to up-regulate COX-2 or COX-2 selective inhibitor NS-398 to inhibit its expression in LoVo cells.the effect of COX-2 onβ-catenin expression was detected by Western blot;using Tanshinone Ⅱ A,PGE₂ and/or GSK-3β selective inhibitor SB-216763 in LoVo cells for 24 h,the effect of Tanshinone ⅡA on COX-2 and P-catenin expression was detected by Western blot;the effect of Tanshinone ⅡA on VEGF expression was detected by ELISA.Results:PGE₂ can increased COX-2 expression,also increased the level of p-catenin in the total cell,cytosolic and nuclear proteinscompared with contrast group.COX-2 selective inhibitor markedly decreased COX-2 expression,also decreased the level of p-catenin in the total cell,cytosolic and nuclear proteins.Tanshinone ⅡA reduced COX-2 and p-catenin protein expression inLoVo cells;Tanshinone Ⅱ can significantly decrease COX-2 and P-catenin protein expression,which were up-regulated by PGE₂.Tanshinone ⅡA decreased VEGF expression and induced- VEGF expression by PGE₂ or GSK-3P selective inhibitor SB-216763.Conclision:Tanshinone ⅡA prevented accumulation of P-catenin,ultimately blocked GSK-3p/p-catenin signal pathway and reduced VEGF expression by inhibiting COX-2 expression,which was one of the possible mechanisms of Tanshinone ⅡA on prevention and treatment of angiogenesis in colon cancer.更多还原