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: Hung-Jen Lin, Shung-Te Kao, Yu-Miao Siao, Chia-Chou Yeh
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 15 Pg. 348 (Oct 07 2015) ISSN: 1472-6882 [Electronic] England
• PMID: 26446078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• NF-kappa B
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein
• JNK Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9

Topics

• Carcinoma, Hepatocellular (drug therapy, metabolism, physiopathology, virology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Drugs, Chinese Herbal (pharmacology)
• Hepatitis B virus (genetics, metabolism)
• Humans
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• Liver Neoplasms (drug therapy, metabolism, physiopathology, virology)
• MAP Kinase Signaling System
• Matrix Metalloproteinase 9 (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphorylation
• Trans-Activators (antagonists & inhibitors, genetics, metabolism)
• Viral Regulatory and Accessory Proteins