Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity  

作　　者：LUO Zhi-yi TIAN Qi CHENG Niang-mei LIU Wen-han YANG Ye CHEN Wei ZHANG Xiang-zhi ZHENG Xiao-yuan CHEN Ming-sheng ZHUANG Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao 

机构地区：[1]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou(350025),China [2]Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development,Zhangzhou Pien Tze Huang Pharmaceutical Co.,Ltd.,Zhangzhou,Fujian Province(363099),China [3]College of Biological Science and Engineering and Mengchao Med-X Center,Fuzhou University,Fuzhou(350116),China [4]Department of Internal Medicine,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou(350025),China

出　　处：《Chinese Journal of Integrative Medicine》2024年第2期115-124,共10页中国结合医学杂志（英文版）

基　　金：Supported by Joint Funds for Innovation of Science and Technology,Fujian Province(No.2019Y9047);Joint Funds for Innovation of Science and Technology of Fujian Province(No.2017Y9117);Young and Middle-Aged Talent Training Project of Fujian Provincial Health and Family Planning Commission(No.2020GGA072);Natural Science Foundation of Fujian Province(No.2020J011164,2020J011170);Startup Fund for Scientific Research,Fujian Medical University(No.2019QH1298);Science and Technology Plan Project of Fuzhou(No.2019-S-87)。

摘　　要：Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 h.Transwell,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),respectively.In vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH.SK-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail vein.Totally 8 mice were randomly divided into PZH and control groups,4 mice in each group.After 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day 17.Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH.Quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq results.Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH.Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylation of YAP was also enhanced by PZH treatment

关 键 词：PienTzeHuang hepatocellular carcinoma RNA-SEQ HIPPO yes-associated protein 

分 类 号：R285[医药卫生—中药学]