基于JAK2/STAT3信号通路探讨白花丹醌对人肝癌细胞迁移和侵袭的影响

Effects of plumbagin on migration and invasion of human hepatoma cell line via JAK2/STAT3 signaling pathway

目的:探讨中药单体白花丹醌(plumbagin,PL)对人肝癌细胞迁移与侵袭的影响及其可能的机制。方法:以人肝癌Huh-7和LM3细胞为研究对象,采用细胞计数试剂盒(CCK-8)法检测不同浓度的PL对Huh-7和LM3细胞增殖的影响,通过划痕实验和Transwell迁移实验检测PL对Huh-7和LM3细胞迁移能力的影响,Transwell侵袭实验检测PL对Huh-7和LM3细胞侵袭能力的影响,Western Blot检测Huh-7和LM3细胞中E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和基质金属蛋白酶-2(MMP-2)及酪氨酸蛋白激酶2(Janus kinase 2,JAK2)/信号传导及转录激活因子3(signal transducer and activator of transcription3,STAT3)信号通路中相关蛋白的表达情况。结果:PL可抑制Huh-7和LM3细胞增殖,且呈现出时间和浓度依赖性;PL以浓度依赖性方式抑制Huh-7和LM3细胞迁移和侵袭;PL可下调N-cadherin、MMP-2蛋白表达,上调E-cadherin蛋白表达,且能够抑制JAK2/STAT3信号通路的激活。结论:PL可抑制人肝癌Huh-7和LM3细胞迁移和侵袭,该过程的分子机制可能与抑制JAK2/STAT3信号通路的激活有关。

Objective:To study the effect of plumbagin(PL)on the migration and invasion of human hepatocellular carcinoma(HCC)cells and its possible mechanism.Methods:The cell counting kit(CCK-8)was used to detect the effects of different concentrations of plumbagin on the proliferation of human hepatocellular carcinoma Huh-7 and LM3 cells.The effect of plumbagin on the migration ability of Huh-7 and LM3 cells was detected by scratch test and Transwell migration test,and the effect of on the invasion ability of Huh-7 and LM3 cells was detected by Transwell invasion test.Western Blot was used to detect the expression of E-cadherin,N-cadherin,matrix metalloproteinase-2 and related proteins in JAK2/STAT3 signaling pathway in Huh-7 and LM3 cells.Results:Plumbagin could inhibit the proliferation of Huh-7 and LM3 cells in a time-and concentration-dependent manner.Plumbagin inhibited the migration and invasion of Huh-7 and LM3 cells in a concentration dependent manner,and it can down-regulate the expression of N-cadherin and MMP-2 protein,up-regulate the expression of E-cadherin protein,and inhibit the activation of JAK2/STAT3 signaling pathway.Conclusion:Plumbagin can inhibit the migration and invasion of human hepatocellular carcinoma Huh-7 and LM3 cells,and the molecular mechanism of this process may be related to the inhibition of JAK2/STAT3 signaling pathway activation.