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没食子儿茶素没食子酸酯通过抑制 EGFR/ERK 通路和细胞周期蛋白 B1/CDK1 复合物诱导人甲状腺未分化癌细胞的生长抑制和凋亡。

Epigallocatechin-3-gallate induces growth inhibition and apoptosis of human anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and cyclin B1/CDK1 complex.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.

出版信息

J Surg Oncol. 2011 Dec;104(7):776-80. doi: 10.1002/jso.21999. Epub 2011 Jul 2.

DOI:10.1002/jso.21999
PMID:21725973
Abstract

BACKGROUND

Anaplastic thyroid carcinoma (ATC) is one of the most lethal cancers because of its aggressiveness and the lack of efficacious therapy. Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, was shown to possess remarkable therapeutic potential against various types of human cancer cells in in vitro and in vivo models. The aim of this study was to investigate the effect of EGCG on the proliferation and apoptosis of ARO cells--human ATC cells.

STUDY DESIGN

Experimental study.

METHODS

Human ATC cell line, ARO, was treated with EGCG. Cell viability was assessed by MTT assay. Inhibition of EGFR/MAPK pathway and cell cycle-related proteins by EGCG were measured by Western blot analysis. In addition, cell cycle analysis was measured by flow cytometry.

RESULTS

EGCG treatment inhibited the growth of ARO cells in a dose-dependent manner. Furthermore, EGCG suppressed phosphorylation of EGFR, ERK1/2, JNK, and p38. These changes were associated with increased p21 and reduced cyclin B1/CDK1 expression. In addition, EGCG treatment increased the accumulation of sub-G1 cell, activated caspase-3 and cleaved PARP.

CONCLUSIONS

Taken together, EGCG inhibits cell proliferation and induces apoptosis via suppression of the EGFR/ERK pathway and cyclin B1/CDK1 complex in ATC cells.

摘要

背景

间变性甲状腺癌(ATC)是最致命的癌症之一,因为它具有侵袭性,而且缺乏有效的治疗方法。儿茶素表没食子酸酯(EGCG)是绿茶中的主要儿茶素,已被证明在体外和体内模型中对多种人类癌细胞具有显著的治疗潜力。本研究旨在探讨 EGCG 对 ARO 细胞(人 ATC 细胞)增殖和凋亡的影响。

研究设计

实验研究。

方法

用 EGCG 处理人 ATC 细胞系 ARO。通过 MTT 分析评估细胞活力。通过 Western blot 分析测量 EGCG 对 EGFR/MAPK 通路和细胞周期相关蛋白的抑制作用。此外,通过流式细胞术测量细胞周期分析。

结果

EGCG 处理以剂量依赖性方式抑制 ARO 细胞的生长。此外,EGCG 抑制了 EGFR、ERK1/2、JNK 和 p38 的磷酸化。这些变化与 p21 的增加和细胞周期蛋白 B1/CDK1 表达的减少有关。此外,EGCG 处理增加了亚 G1 细胞的积累,激活了 caspase-3 和裂解的 PARP。

结论

综上所述,EGCG 通过抑制 ATC 细胞中的 EGFR/ERK 通路和细胞周期蛋白 B1/CDK1 复合物来抑制细胞增殖并诱导细胞凋亡。

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