芦荟大黄素抑制肝癌细胞增殖与迁移的机制  

Mechanism of aloe-emodin in inhibiting proliferation and migration of hepatocellular carcinoma cells

作　　者：谭章斌 徐由财 丁文俊 邓穗晖 刘彬[1] 张竞之[1] TAN Zhang-bin;XU You-cai;DING Wen-jun;DENG Sui-hui;LIU Bin;ZHANG Jing-zhi(Department of Traditional Chinese Medicine,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China)

机构地区：[1]广州医科大学附属第二医院中医科,广东广州510260

出　　处：《中成药》2021年第10期2653-2658,共6页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(82004104);中国博士后科学基金项目(2020M682678);广东省基础与应用基础研究基金项目(2019A1515110367)。

摘　　要：目的探索芦荟大黄素抑制肝癌细胞的潜在作用机制。方法通过MTS、平板克隆形成、EdU染色观察芦荟大黄素对SMMC-7721和Hep3B肝癌细胞增殖的影响,Transwell细胞迁移实验观察芦荟大黄素对SMMC-7721细胞迁移的影响,Western blot观察肝癌细胞内Src/STAT3信号通路相关蛋白的表达,通过分子对接、分子动力学模拟和表面等离子共振技术,进一步研究芦荟大黄素与Src之间的结合作用。结果芦荟大黄素以浓度依赖性的方式抑制肝癌细胞增殖与迁移能力。Western blot结果提示,芦荟大黄素抑制肝癌细胞内Src/STAT3信号通路的激活以及下游增殖和迁移相关蛋白表达。分子对接、分子动力学模拟和表面等离子共振提示,芦荟大黄素与Src具有很强的结合能力。结论芦荟大黄素是一种有效的抗肝癌药物,通过抑制Src/STAT3信号通路抑制肝癌细胞增殖与迁移。AIM To explore the potential mechanism of aloe-emodin in inhibiting hepatocellular carcinoma(HCC) cells.METHODS The effects of aloe-emodin on the proliferation of SMMC-7721 and Hep3 B HCC cells were observed by MTS,colony formation assays and EdU staining;its impact on the migration of SMMC-7721 cells were observed by transwell cell migration experiments. Western blot was used to detect the expressions of Src/STAT3 signaling pathway related proteins in HCC cells. Molecular docking, molecular dynamics simulations and surface plasmon resonance were applied to highlighting the interactions between aloe-emodin and the Src protein.RESULTS The results showed that aloe-emodin inhibited the proliferation and migration of HCC cells in a concentration-dependent manner. Western blot revealed that aloe-emodin inhibited the activation of Src/STAT3 signaling pathway, and the expressions of downstream proliferation-related proteins Cyclin D1, c-Myc, and migration-related proteins MMP-9 and MMP-2. The strong binding ability of aloe-emodin to Src was suggested by molecular docking, molecular dynamics simulations and surface plasmon resonance.CONCLUSION Aloe-emodin is an effective drug to combat HCC because of its efficacy in inhibiting the proliferation and migration of HCC cells via Src/STAT3 signaling pathway.

关 键 词：芦荟大黄素 肝癌 Src/STAT3信号通路 增殖 迁移 

分 类 号：R285.5[医药卫生—中药学]