title: The Chinese medicine Sini-San inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells.
abstract: BACKGROUND
  Sini-San (SNS) is a formulation of four Traditional Chinese Drugs that exhibits beneficial therapeutic effects in liver injury and hepatitis. However, there are no reports describing its effects on the hepatitis B X-protein (HBx)-induced invasion and metastasis in hepatoma cells, and the detailed molecular mechanisms of its actions are still unclear.
  
  
  METHODS
  In this study, we investigated the mechanisms underlying SNS-mediated inhibition of HBx-induced cell invasion and the inhibition of secreted and cytosolic MMP-9 production, using gelatin zymography and Western blot analysis in a human hepatoma cell line (HepG2). Relative luciferase activity was assessed for MMP-9, NF-κB, or AP-1 reporter plasmid-transfected cells.
  
  
  RESULTS
  SNS suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κ B (NF-κB) activity. SNS suppressed HBx-induced AP-1 activity through inhibition of phosphorylation in the extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. SNS also suppressed HBx-induced inhibition of NF-κB nuclear translocation through IκB and suppressed HBx-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1.
  
  
  CONCLUSIONS
  SNS suppresses the invasiveness and metastatic potential of hepatocellular carcinoma cells by inhibiting multiple signal transduction pathways.
authors.affiliation: Department of Traditional Chinese Medicine Diagnosis, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Division of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.affiliation: Department of Chinese Medicine, Buddhist Dalin Tzu Chi General Hospital, Min-Sheng Road, Dalin Town, Chia-Yi, 62247, Taiwan.
authors.forename: Yu-Miao
authors.initials: YM
authors.lastname: Siao
authors.affiliation: School of Post-baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan. yehcc0530@gmail.com.|Department of Chinese Medicine, Buddhist Dalin Tzu Chi General Hospital, Min-Sheng Road, Dalin Town, Chia-Yi, 62247, Taiwan. yehcc0530@gmail.com.
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004365:Drugs, Chinese Herbal; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein