首页|Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity
Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity
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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 x 103 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-8 and 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 μ g/mL for SK-Hep-1 cells and 330 μ g/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(106 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 in vitro and in vivo.Furthermore,PZH played roles in inhibiting the transcriptional activity of YAP.Conclusion:PZH restrained migration,invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.
Pien Tze Huanghepatocellular carcinomaRNA-seqHippoyes-associated protein
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou(350025),China
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
College of Biological Science and Engineering and Mengchao Med-X Center,Fuzhou University,Fuzhou(350116),China
Department of Internal Medicine,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou(350025),China
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Joint Funds for Innovation of Science and Technology,Fujian ProvinceJoint Funds for Innovation of Science and Technology of Fujian ProvinceYoung and Middle-Aged Talent Training Project of Fujian Provincial Health and Family Planning CommissionNatural Science Foundation of Fujian ProvinceNatural Science Foundation of Fujian ProvinceStartup Fund for Scientific Research,Fujian Medical UniversityScience and Technology Plan Project of Fuzhou
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