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

Lin HJ, Kao ST, Siao YM, Yeh CC - BMC Complement Altern Med (2015)

Bottom Line: Sini-San (SNS) is a formulation of four Traditional Chinese Drugs that exhibits beneficial therapeutic effects in liver injury and hepatitis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine Diagnosis, China Medical University Hospital, Taichung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of SNS on TPA-induced NF-κB and AP-1 activation in HepG2 cell. EMSAs were performed on nuclear extracts following HBx-induced NF-κB (a) and AP-1 (b) activation. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS for 1 h, then treated with DOX for 45 min, followed by nuclear extract preparation
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Fig5: Effect of SNS on TPA-induced NF-κB and AP-1 activation in HepG2 cell. EMSAs were performed on nuclear extracts following HBx-induced NF-κB (a) and AP-1 (b) activation. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS for 1 h, then treated with DOX for 45 min, followed by nuclear extract preparation

Mentions: To determine whether the inhibitory effect of SNS in HBx-treated cells leads to NF-κB and AP-1 inhibition, the effects of SNS on HBx-stimulated NF-κB- and AP-1-specific DNA binding activity were examined. Using biotinylated EMSAs, HBx was shown to increase DNA binding of NF-κB and AP-1 after 45 min. Treatment with 400 and 800 μg/ml SNS inhibited HBx-induced DNA binding by NF-κB and AP-1 (Fig. 5a, b).Fig. 5


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

Lin HJ, Kao ST, Siao YM, Yeh CC - BMC Complement Altern Med (2015)

Effect of SNS on TPA-induced NF-κB and AP-1 activation in HepG2 cell. EMSAs were performed on nuclear extracts following HBx-induced NF-κB (a) and AP-1 (b) activation. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS for 1 h, then treated with DOX for 45 min, followed by nuclear extract preparation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597375&req=5

Fig5: Effect of SNS on TPA-induced NF-κB and AP-1 activation in HepG2 cell. EMSAs were performed on nuclear extracts following HBx-induced NF-κB (a) and AP-1 (b) activation. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS for 1 h, then treated with DOX for 45 min, followed by nuclear extract preparation
Mentions: To determine whether the inhibitory effect of SNS in HBx-treated cells leads to NF-κB and AP-1 inhibition, the effects of SNS on HBx-stimulated NF-κB- and AP-1-specific DNA binding activity were examined. Using biotinylated EMSAs, HBx was shown to increase DNA binding of NF-κB and AP-1 after 45 min. Treatment with 400 and 800 μg/ml SNS inhibited HBx-induced DNA binding by NF-κB and AP-1 (Fig. 5a, b).Fig. 5

Bottom Line: Sini-San (SNS) is a formulation of four Traditional Chinese Drugs that exhibits beneficial therapeutic effects in liver injury and hepatitis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine Diagnosis, China Medical University Hospital, Taichung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus