丹参酮ⅡA对COX-2激活Wnt/β-catenin信号通路介导的人肠癌细胞VEGF表达的调控作用  

Effect of Tanshinone Ⅱ A on COX-2-β-catenin signal transduction pathway-mediated VEGF expression in human colorectal cancer cells

作　　者：刘宣[1] 王炎[1] 李丹光 周利红[1] 殷佩浩[1] 隋华[1] 范忠泽[1] 李琦[1,3] 

机构地区：[1]上海中医药大学附属普陀医院,上海200062 [2]吉林省肿瘤医院,长春130012 [3]上海中医药大学附属曙光医院,上海201203

出　　处：《中华中医药杂志》2013年第1期108-112,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：上海市自然科学基金资助项目(No.10ZR1427400;No.09ZR1428500);上海市第六院医疗集团项目(No.20114001);上海市教委科研创新项目(No.12YZ058);上海市中医药科研基金(No.2011ZJ030);上海市普陀区科委重点项目(No.2010PTKW005)~~

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。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.

关 键 词：结肠癌 丹参酮ⅡA 环氧化酶-2 WNT Β-CATENIN信号通路 血管内皮生长因子 

分 类 号：R735.34[医药卫生—肿瘤]