The Chinese medicine Sini-San inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells

• Published in: BMC complementary and alternative medicine 2015-10, Vol.15 (1), p.348-348, Article 348
• Main Authors: Lin, Hung-Jen, Kao, Shung-Te, Siao, Yu-Miao, Yeh, Chia-Chou
• Format: Article
• Language: English
• Subjects: Analysis; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - physiopathology; Carcinoma, Hepatocellular - virology; Care and treatment; Cell Line, Tumor; Cell Movement - drug effects; Complications and side effects; Development and progression; Drugs, Chinese Herbal - pharmacology; Genetic aspects; Health aspects; Hepatitis B; Hepatitis B virus - genetics; Hepatitis B virus - metabolism; Humans; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Liver; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - physiopathology; Liver Neoplasms - virology; MAP Kinase Signaling System; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medicine, Oriental; Metastasis; NF-kappa B - genetics; NF-kappa B - metabolism; Patient outcomes; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Risk factors; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 1472-6882; 1472-6882
• DOI: 10.1186/s12906-015-0870-6

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. 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. 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. SNS suppresses the invasiveness and metastatic potential of hepatocellular carcinoma cells by inhibiting multiple signal transduction pathways.