Effects and mechanisms of silibinin on human hepatoma cell lines
Effects and mechanisms of silibinin on human hepatoma cell lines
复制标题
DOI：
10.3748/wjg.v13.i40.5299
复制
发表时间：
2007-10-28
影响因子：
4.3
通讯作者：
Hu, Ke-Qin
中科院分区：
文献类型：
--
作者：
Lah, John J.;Cui, Wei;Hu, Ke-Qin
目的：目的：探讨水飞蓟宾对肝癌细胞生长的影响及其机制。水飞蓟宾对肝癌细胞的生长和增殖，凋亡，细胞周期进程，组蛋白乙酰化，和其他相关的信号transduces.Results的影响：我们证明，水飞蓟宾显着降低HuH 7，HepG 2，Hep 3B，和PLC/PRF/5人肝癌细胞的生长。水飞蓟宾降低HuH 7细胞生长与显著上调p21/CDK 4和p27/CDK 4复合物，下调Rb磷酸化和E2 F1/DP 1复合物相关。水飞蓟宾促进HuH 7细胞凋亡与clohn调节的survivin和上调活化的caspase-3和-9有关。水飞蓟宾的抗血管生成作用通过下调金属蛋白酶2（MMP 2）和CD 34来表示。我们发现，水飞蓟宾降低的HuH 7细胞生长与第十号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）的活性增加和p-Akt产生减少相关，表明PTEN/PI 3 K/Akt途径在水飞蓟宾介导的抗HCC效应中的作用。我们还表明，水飞蓟宾增加组蛋白H3和H4（AC-H3和AC-H4）的乙酰化，表明改变组蛋白乙酰化在水飞蓟宾减少肝癌细胞proliferation.CONCLUSION：我们的研究结果定义了水飞蓟宾的体外抗肝癌作用和可能的机制，并提供了一个合理的进一步测试水飞蓟宾肝癌化学预防。(C)2007年WJG。All rights reserved.
AIM: To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma (HCC) cell growth.METHODS: Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined.RESULTS: We demonstrated that silibinin significantly reduced the growth of HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly up-regulated p21/CDK4 and p27/CDK4 complexes, down-regulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with clown-regulated survivin and upregulated activated caspase-3 and -9. Silibinin's antiangiogenic effects were indicated by down-regulated metalloproteinase-2 (MMP2) and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and decreased p-Akt production, indicating the role of PTEN/PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 (AC-H3 and AC-H4), indicating a possible role of altered histone acetylation in silibinin-reduced HCC cell proliferation.CONCLUSION: Our results defined silibinin's in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention. (C) 2007 WJG. All rights reserved.