The Chinese medicine Sini-San inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells.
The Chinese medicine Sini-San inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells.
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DOI：
10.1186/s12906-015-0870-6
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发表时间：
2015-10-07
影响因子：
--
通讯作者：
Yeh CC
中科院分区：
文献类型：
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作者：
Lin HJ;Kao ST;Siao YM;Yeh CC
四味散（SNS）是由四种中药组成，对肝损伤和肝炎有良好的治疗作用。然而，目前尚无报道描述其对乙型肝炎x蛋白（HBx）诱导的肝癌细胞侵袭和转移的影响，其作用的详细分子机制尚不清楚。在这项研究中，我们在人肝癌细胞系（HepG2）中使用明胶酶谱法和Western blot分析，研究了sns介导的抑制hbx诱导的细胞侵袭和抑制分泌和胞质MMP-9产生的机制。检测转染MMP-9、NF-κB或AP-1报告细胞的荧光素酶相对活性。SNS通过抑制激活蛋白(AP)-1和核因子-κB （NF-κB）活性来抑制MMP-9的转录。SNS通过抑制胞外信号相关激酶（ERK）和c-Jun n -末端激酶（JNK）信号通路的磷酸化来抑制hbx诱导的AP-1活性。SNS还通过i -κB抑制hbx诱导的NF-κB核易位抑制，抑制hbx诱导的NF-κB和AP-1上游ERK/磷脂酰肌醇3-激酶/Akt的活化。SNS通过抑制多种信号转导途径抑制肝癌细胞的侵袭性和转移潜能。
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.