摘要
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 down-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 silibininreduced 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.
瞄准：在肝细胞上调查在试管内效果和 silibinin 的机制癌(HCC ) 细胞生长。方法：人的 HCC 房间线与 silibinin 的不同剂量被对待。HCC 房间生长和增长上的 silibinin 的效果， apoptosis，房间周期前进，嘘一乙酰化作用，和另外的相关信号 transductions 系统地被检验。结果：我们证明 silibinin 显著地减少了 HuH7， HepG2， Hep3B，和 PLC/PRF/5 人的生长肝细胞瘤细胞。减少 Silibinin 的 HuH7 房间生长与显著地起来调整的 p21/CDK4 和 p27/CDK4 建筑群被联系，下面调整的 Rb-phosphorylation 和 E2F1/DP1 建筑群。Silibinin 支持了与下面调整的 survivin 和起来调整的激活的 caspase-3 和 -9 被联系的 HuH7 房间的 apoptosis。Silibinin 的 anti-angiogenic 效果被下面调整的 metalloproteinase-2 (MMP2 ) 和 CD34 显示。我们发现 HuH7 细胞的减少 silibinin 的生长与磷酸酶的增加的活动被联系，十在染色体十上在相当或相同的事物删除了(PTEN ) 并且减少的 p-Akt 生产，在调停 silibinin 的 anti-HCC 显示 PTEN/PI3K/Akt 小径的角色完成。我们也证明 silibinin 增加了乙酰化作用嘘一 H3 和 H4 (AC-H3 和 AC-H4 ) ，显示一个可能的角色改变嘘在减少 silibinin 的 HCC 房间增长的一乙酰化作用。结论：我们的结果定义 silibinin 的在试管内 anti-HCC 效果和可能的机制，并且提供了一个基本原理进一步为 HCC chemoprevention 测试 silibinin。
基金
Supported by UCI institutional research grants from GI Division Chao Family Comprehensive Cancer Center(K.-Q.H.)
