白茅苷抑制β-catenin/TCF4通路的活化对肝癌HepG2细胞增殖、侵袭和间质转化的调节作用  

Imperatorin inhibits the activation ofβ-catenin/TCF4 pathway to regulate the proliferation,invasion and mesenchymal transition of hepatocellular carcinoma HepG2 cells

作　　者：赵伶伶 郭静波[2] 白冬梅 杨晓晴 杜可新 ZHAO Ling-ling;GUO Jing-bo;BAI Dong-mei;YANG Xiao-qing;DU Ke-xin(Department of oncology,Tieling Central Hospital,Tieling,112000,China;Hospice ward of Shengjing Hospital Affiliated to China Medical University,Shenyang,110000,China;Department of oncology,Panjin Central Hospital,Panjin,124000,China)

机构地区：[1]铁岭市中心医院肿瘤内科,112000 [2]中国医科大学附属盛京医院宁养病房,110000 [3]盘锦市中心医院肿瘤内三科,124000

出　　处：《现代消化及介入诊疗》2020年第12期1606-1610,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：辽宁省自然基金资助项目(201602815)

摘　　要：目的研究白茅苷(Imp)对肝癌HepG2细胞增殖、侵袭和间质转化的调节作用及其作用机制。方法体外实验:将细胞随机分为Control组、Imp(50μmol/L)组、Imp(100μmol/L)组和Imp(200μmol/L)组,给予对应处理后,通过Brdu染色、Transwell、划痕实验和Western blot分别检测肝癌HepG2细胞增殖、侵袭、迁移能力、上皮间质转化相关蛋白和信号通路蛋白表达情况;体内实验:皮下注射肝癌HepG2细胞建立肝癌移植瘤模型,给予对应处理后记录各组肿瘤体积,并通过免疫组化检测肿瘤组织Ki67和血管内皮生长因子(VEGF)表达。结果Imp剂量依赖性地抑制体外培养的肝癌HepG2细胞增殖和Ki67、PCNA表达量(P<0.05),侵袭细胞数(P<0.05),划痕闭合率(P<0.05);调节VEGF、E-钙黏蛋白(E-cadherin)和N-钙黏蛋白(N-cadherin)表达(P<0.05);下调β-catenin、TCF4和c-Myc相对蛋白表达(P<0.05)。Imp剂量依赖性地抑制移植瘤肿瘤生长体积(P<0.05)和肿瘤组织中增殖相关蛋白Ki67、PCNA表达(P<0.05)。结论Imp能抑制肝癌HepG2细胞体外增殖、侵袭和间质转化能力及移植瘤的体内生长,其机制与抑制β-catenin/TCF4通路活化相关。Objective To study the regulatory effect of Imperatorin(Imp)on proliferation,invasion and mesenchymal transformation of hepatocellular carcinoma HepG2 cells and its mechanism.Methods In vitro experiment:The cells were randomly divided into control group,Imp(50μM),Imp(100μM)group and Imp(200μM)group.After corresponding treatment,the proliferation,invasion,migration,epithelial-mesenchymal transition(EMT)related proteins and signaling pathway proteins of HepG2 cells were detected by Brdu staining,Transwell,scratch test and Western blot,respectively.In vivo experiments:HepG2 cells were injected subcutaneously to establish the transplanted tumor model of hepatocellular carcinoma,and the tumor volume of each group was recorded,The expression of Ki67 and VEGF were detected by immunohistochemistry.Results In vitro experiments:Imp inhibited HepG2 cells proliferation,expression of proliferation-related protein Ki67 and PCNA(P<0.05),numbers of invasive cells(P<0.05)and scratch closure rate(P<0.05)in dose-dependent manner;regulated vascular endothelial growth factor(VEGF),E-cadherin and N-cadherin expression(P<0.05);down-regulated the relative protein expression ofβ-catenin,TCF4 and c-Myc(P<0.05).In vivo:Imp dose-dependent inhibited tumor growth volume(P<0.05)and expression of Ki67 and PCNA in tumor tissue(P<0.05).Conclusion Imp could inhibit the proliferation,invasion and mesenchymal transition of HepG2 cells in vitro and the growth of transplanted tumors in vivo.Its mechanism is related to inhibiting the activation of theβ-catenin/TCF4 pathway.

关 键 词：白茅苷 肝癌HEPG2细胞 间质转化 细胞侵袭 C-MYC 

分 类 号：R575.5[医药卫生—消化系统]