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(-)-表没食子儿茶素-3-没食子酸酯抑制人结直肠癌的肝转移。

(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer.

机构信息

Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

出版信息

Oncol Rep. 2014 Feb;31(2):625-33. doi: 10.3892/or.2013.2925. Epub 2013 Dec 13.

DOI:10.3892/or.2013.2925
PMID:24337301
Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer. The aim of the present study was to elucidate the potential use of EGCG as chemotherapy targeting liver metastases of human colorectal cancer. To assess the effect of EGCG on human colorectal cancer cell lines, RKO and HCT116, cell viability, cell proliferation and apoptosis were measured by cell counting kit-8, BrdU assay and TUNEL staining, respectively. Protein and gene expression were measured by western blot analysis and RT-PCR analysis, respectively. EGCG inhibited cell proliferation and induced apoptosis. EGCG dephosphorylated constitutively activated Akt and increased the activation of p38. EGCG also decreased the expression of vascular endothelial growth factor receptor 2. Additionally, the ability of EGCG to prevent the development of liver metastases of RKO tumors was evaluated in SCID mice. EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration. Our findings indicate that EGCG may be useful in the treatment of liver metastases of human colorectal cancer.

摘要

(-)-表没食子儿茶素没食子酸酯(EGCG)是绿茶的主要成分,已被证明可抑制几种类型的人类肿瘤细胞增殖并诱导细胞凋亡。结直肠癌最常见的远处转移部位是肝脏。然而,以前没有研究报道 EGCG 具有抑制人结直肠癌肝转移的能力。本研究旨在阐明 EGCG 作为针对人结直肠癌肝转移的化疗药物的潜在用途。为了评估 EGCG 对人结直肠癌细胞系 RKO 和 HCT116 的影响,通过细胞计数试剂盒-8、BrdU 测定和 TUNEL 染色分别测量细胞活力、细胞增殖和细胞凋亡。通过 Western blot 分析和 RT-PCR 分析分别测量蛋白质和基因表达。EGCG 抑制细胞增殖并诱导细胞凋亡。EGCG 使持续激活的 Akt 去磷酸化,并增加 p38 的激活。EGCG 还降低了血管内皮生长因子受体 2 的表达。此外,还在 SCID 小鼠中评估了 EGCG 预防 RKO 肿瘤肝转移发展的能力。EGCG 抑制了肝转移中的血管生成并诱导了细胞凋亡,而没有伴随体重减轻或肝毒性。此外,EGCG 给药显著减少了肝转移面积。我们的研究结果表明,EGCG 可能对治疗人结直肠癌肝转移有用。

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