丹参酮ⅡA通过EP2调控β-arrestin/β-catenin信号通路抑制大肠癌侵袭转移机制

Tanshinone ⅡA inhibits invasion and metastasizing of colorectal cancer by EP2 regulating β-arrestin/β-catenin signaling pathway

目的:探讨丹参酮ⅡA对大肠癌细胞转移能力的影响及可能的作用机制。方法:利用CCK-8检测不同浓度丹参酮ⅡA对人结肠癌LoVo细胞增殖的影响;采用transwell、划痕实验研究丹参酮ⅡA对人结肠癌LoVo细胞侵袭转移能力的影响;利用Western Blot研究丹参酮ⅡA对EP2介导的β-arrestin/β-catenin信号传递轴的影响。结果:丹参酮ⅡA能够以剂量和时间依赖性方式抑制人结肠癌LoVo细胞的增殖;EP2能够促进LoVo细胞的侵袭转移能力(P<0.01),上调β-arretin的表达,进一步促进β-catenin的核转移(P<0.01);与空白对照组比较,丹参酮ⅡA能够明显抑制LoVo细胞的侵袭转移能力且呈剂量依赖性(P<0.01);同时,丹参酮ⅡA能够直接下调EP2受体的表达,抑制β-arretin的激活,进一步抑制β-catenin的核转移(P<0.01)。结论:丹参酮ⅡA能够抑制EP2/β-arrestin信号通路的激活,从而阻断β-catenin信号通路,发挥抗大肠癌侵袭转移的作用。

Objective:To investigate the effect of tanshinoneⅡA on the metastatic ability of colorectal cancer cells and its possible mechanism.Methods:The effects of different concentrations of tanshinoneⅡA on the proliferation of human colon cancer LoVo cells were detected by CCK-8.The effects of tanshinoneⅡA on the invasion and metastasis of human colon cancer LoVo cells were studied by transwell and scratch test.Western Blot were used to investigate the effect of tanshinoneⅡA on EP2-mediatedβ-arrestin/β-catenin signaling axis.Results:TanshinoneⅡA inhibited the proliferation of human colon cancer LoVo cells in a dose-and time-dependent manner.EP2 promoted the invasion and metastasis of LoVo cells(P<0.01),up-regulated the expression ofβ-arretin,and further promoted the nuclear transfer ofβ-catenin(P<0.01);compared with the blank control group,tanshinoneⅡA could significantly inhibit the invasion and metastasis of LoVo cells in a dose-dependent manner(P<0.01).Meanwhile,tanshinoneⅡA could directly down-regulate the expression of EP2 receptor and inhibit activation ofβ-arretin so as to further inhibited nuclear transfer ofβ-catenin(P<0.01).Conclusion:TanshinoneⅡA can inhibit the activation of EP2/β-arrestin signaling pathway,thereby blocking theβ-catenin signaling pathway and exerting its role in the invasion and metastasis of colorectal cancer.