Nishikawa T, Nakajima T, Moriguchi M, Jo M, Sekoguchi S, Ishii M, Takashima H, Katagishi T, Kimura H, Minami M, Itoh Y, Kagawa K, Okanoue T
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
J Hepatol. 2006 Jun;44(6):1074-82. doi: 10.1016/j.jhep.2005.11.045. Epub 2005 Dec 28.
BACKGROUND/AIMS: A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects on hepatocellular carcinomas (HCCs).
Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed.
EGCG inhibited the growth of all HCC cell lines at concentrations of 50-100 microg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2alpha and Bcl-xl by inactivation of NF-kappaB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells.
EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.
背景/目的：绿茶的一种主要多酚成分，表没食子儿茶素-3-没食子酸酯（EGCG），此前已被证明可在多种癌症中诱导细胞周期停滞和凋亡。然而，其对肝细胞癌（HCC）的影响却知之甚少。
用EGCG或溶剂处理四种肝癌细胞系，即HLE、HepG2、HuH-7和PLC/PRF/5。通过台盼蓝染色和WST-8测定评估细胞活力。通过流式细胞术和蛋白质印迹法评估HLE细胞中的细胞周期、凋亡及凋亡相关蛋白。还使用异种移植模型在体内研究了EGCG的作用。同时评估了EGCG与肿瘤坏死因子相关凋亡诱导配体（TRAIL）联合处理的效果。
EGCG在浓度为50 - 100μg/ml时可抑制所有肝癌细胞系的生长。在HLE细胞中，EGCG诱导凋亡但不引起细胞周期停滞，且似乎通过使NF-κB失活而下调了Bcl-2α和Bcl-xl。口服EGCG在HLE异种移植肿瘤中显示出类似的效果。EGCG与TRAIL联合处理可协同诱导HLE细胞凋亡。
EGCG在体外和体内均可诱导HLE细胞凋亡。此外，它还增强了TRAIL诱导的凋亡。因此，EGCG治疗可能有助于改善肝癌的预后。
