School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
BMC Complement Altern Med. 2014 Jan 16;14:26. doi: 10.1186/1472-6882-14-26.
Genistein (Gen) exhibits anti-mutagenic and anti-metastatic activities in hepatoma cell lines. Gen has suppressive effects on tumor growth and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive activity on hepatocellular carcinoma (HCC) cells is unclear.
In this study, the possible mechanisms underlying Gen-mediated reduction of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2) were investigated.
Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κ B (NF-κB) activity. Gen suppressed TPA-induced AP-1 activity through inhibitory phosphorylation of extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA-stimulated inhibition of NF-κB nuclear translocation through IκB inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1.
Gen and its inhibition of multiple signal transduction pathways can control the invasiveness and metastatic potential of HCC.
染料木黄酮（Gen）在肝癌细胞系中表现出抗诱变和抗转移活性。Gen 对裸鼠肿瘤生长和血管生成具有抑制作用。Gen 抑制基质金属蛋白酶（MMP）-9 的酶活性；然而，其对肝癌细胞（HCC）细胞的抗侵袭活性的机制尚不清楚。
在这项研究中，研究了 Gen 介导的减少 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的细胞侵袭和抑制人肝癌细胞（HepG2、Huh-7 和 HA22T）和鼠胚胎肝细胞（BNL CL2）中分泌型和胞浆型 MMP-9 产生的可能机制。
Gen 通过抑制激活蛋白（AP）-1 和核因子-κB（NF-κB）活性来抑制 MMP-9 转录。Gen 通过抑制细胞外信号相关激酶（ERK）和 c-Jun N-末端激酶（JNK）信号通路的磷酸化来抑制 TPA 诱导的 AP-1 活性，并通过 IκB 抑制信号通路抑制 TPA 刺激的 NF-κB 核易位。此外，Gen 抑制了 TPA 诱导的 NF-κB 和 AP-1 上游 ERK/磷酸肌醇 3-激酶/Akt 的激活。
Gen 及其对多种信号转导通路的抑制作用可以控制 HCC 的侵袭性和转移潜力。
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