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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 HBx-induced, MAPK, IκB, and AKT- signaling pathways. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS before incubation with DOX for 45 min. Whole-cell lysates were then prepared and subjected to Western blot analysis using antibodies specific for phosphorylated PI3k, AKT, IκB, JNK, p38, and ERK in Western blot
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Fig6: Effect of SNS on HBx-induced, MAPK, IκB, and AKT- signaling pathways. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS before incubation with DOX for 45 min. Whole-cell lysates were then prepared and subjected to Western blot analysis using antibodies specific for phosphorylated PI3k, AKT, IκB, JNK, p38, and ERK in Western blot

Mentions: MAPKs are known to regulate AP-1 and NF-κB activation via multiple mechanisms. Studies have shown that the MAPK, IκB, and PI3K/Akt signaling pathways are involved in HBx-mediated induction of MMP-9 [9, 37–39]. Therefore, we investigated the effects of SNS on HBx-induced phosphorylation of ERK, p38, JNK, IκB, and PI3K/Akt activity in HepG2 cells. Western blot analysis revealed that HBx expression alone caused a significant increase in the phosphorylation of ERK, p38, JNK, IκB, PI3K, and Akt compared to vehicle-treated controls; this phosphorylation was blocked by pre-treatment with SNS (Fig. 6). HBx-induced phosphorylation of MAPK, IκB, and PI3K/Akt was inhibited in cells treated with 400 and 800 μg/ml SNS.Fig. 6


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 HBx-induced, MAPK, IκB, and AKT- signaling pathways. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS before incubation with DOX for 45 min. Whole-cell lysates were then prepared and subjected to Western blot analysis using antibodies specific for phosphorylated PI3k, AKT, IκB, JNK, p38, and ERK in Western blot
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4597375&req=5

Fig6: Effect of SNS on HBx-induced, MAPK, IκB, and AKT- signaling pathways. HepG2-HBx-GFP cells were pretreated with 200–800 μg/ml SNS before incubation with DOX for 45 min. Whole-cell lysates were then prepared and subjected to Western blot analysis using antibodies specific for phosphorylated PI3k, AKT, IκB, JNK, p38, and ERK in Western blot
Mentions: MAPKs are known to regulate AP-1 and NF-κB activation via multiple mechanisms. Studies have shown that the MAPK, IκB, and PI3K/Akt signaling pathways are involved in HBx-mediated induction of MMP-9 [9, 37–39]. Therefore, we investigated the effects of SNS on HBx-induced phosphorylation of ERK, p38, JNK, IκB, and PI3K/Akt activity in HepG2 cells. Western blot analysis revealed that HBx expression alone caused a significant increase in the phosphorylation of ERK, p38, JNK, IκB, PI3K, and Akt compared to vehicle-treated controls; this phosphorylation was blocked by pre-treatment with SNS (Fig. 6). HBx-induced phosphorylation of MAPK, IκB, and PI3K/Akt was inhibited in cells treated with 400 and 800 μg/ml SNS.Fig. 6

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