Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway.
Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway.
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DOI：
10.1371/journal.pone.0072927
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Chen K;Zhang S;Ji Y;Li J;An P;Ren H;Liang R;Yang J;Li Z
黄芩素是一种广泛使用的中草药，历史上曾用于抗炎和抗癌治疗。然而，黄芩素对肝细胞癌（HCC）的抗转移作用及其分子机制尚不清楚。因此，本研究的目的是评估黄芩素抗肝癌转移的作用及其相关机制。基于在肝癌细胞系和动物模型中使用的测定，我们发现黄芩素在体内和体外抑制肿瘤细胞转移。黄芩素作用24 h后，MHCC 97 H细胞基质金属蛋白酶2（MMP-2）、MMP-9和尿激酶型纤溶酶原激活物（u-PA）的表达水平及蛋白酶活性均下降。同时，TIMP-1和TIMP-2的表达呈剂量依赖性增加。此外，黄芩素治疗显着降低磷酸化形式的MEK 1和ERK 1/2的水平。MEK 1过表达部分阻断黄芩素的抗转移作用。ERK抑制剂（U 0126）与黄芩素联合作用可协同降低MMP-2、MMP-9和u-PA的表达，增加TIMP-1和TIMP-2的表达，抑制MHCC 97 H细胞的侵袭能力。总之，黄芩素通过抑制ERK通路降低细胞运动和迁移来抑制肿瘤细胞的侵袭和转移，表明黄芩素是一种潜在的肝癌治疗剂。
Baicalein, a widely used Chinese herbal medicine, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain poorly understood. Therefore, the purpose of this study was to assess the anti-metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays utilized in both HCC cell lines and in an animal model, we found that baicalein inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after treatment with baicalein for 24 hours, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (u-PA) expression as well as proteinase activity in hepatocellular carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent fashion. Moreover, baicalein treatment dramatically decreased the levels of the phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked the anti-metastatic effects of baicalein. Combined treatment with an ERK inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP-9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the invasive capabilities of MHCC97H cells were also inhibited. In conclusion, baicalein inhibits tumor cell invasion and metastasis by reducing cell motility and migration via the suppression of the ERK pathway, suggesting that baicalein is a potential therapeutic agent for HCC.
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影响因子：
3.7
作者：
Liu B;Wang G;Yang J;Pan X;Yang Z;Zang L
通讯作者：
Zang L
影响因子：
5.2
作者：
Liang, Rong-Rui;Zhang, Shu;Li, Zong-Fang
通讯作者：
Li, Zong-Fang
影响因子：
2.9
作者：
Chen, CH;Huang, LLH;Lu, FJ
通讯作者：
Lu, FJ
益气扶生中药配方通过抑制 ERK/MAPK 信号通路的激活，下调 MMP-2/9 来抑制结直肠癌的迁移/侵袭。
影响因子：
--
作者：
Deng W;Sui H;Wang Q;He N;Duan C;Han L;Li Q;Lu M;Lv S
通讯作者：
Lv S
影响因子：
64.8
作者：
ANDERSON, NG;MALLER, JL;STURGILL, TW
通讯作者：
STURGILL, TW