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低浓度的(-)-表没食子儿茶素没食子酸酯(EGCG)与姜黄素联合使用,通过引起细胞周期停滞,在体外和体内均能强烈抑制非小细胞肺癌的生长。

Combination of low concentration of (-)-epigallocatechin gallate (EGCG) and curcumin strongly suppresses the growth of non-small cell lung cancer in vitro and in vivo through causing cell cycle arrest.

作者信息

Zhou Dong-Hu, Wang Xuemin, Yang Mingmin, Shi Xiaoyan, Huang Wenbin, Feng Qing

机构信息

Department of Nutrition and Food Safety, Nanjing Medical University, Nanjing 211166, Jiangsu, China.

出版信息

Int J Mol Sci. 2013 Jun 5;14(6):12023-36. doi: 10.3390/ijms140612023.

Abstract

(-)-Epigallocatechin gallate (EGCG) and curcumin are two naturally derived agents that have been widely investigated worldwide. They exhibit their anti-tumor effects in many types of cancers. In the current study, the effect of the combination of the two agents on non-small cell lung cancer (NSCLC) cells was investigated. The results revealed that at low concentrations, the combination of the EGCG and curcumin strongly enhanced cell cycle arrest. Flow cytometry analysis showed that the cells were arrested at G1 and S/G2 phases. Two main cell cycle related proteins cyclin D1 and cyclin B1 were significantly inhibited at the present of EGCG and curcumin. EdU (5-ethynyl-2'-deoxyuridine) fluorescence staining showed that the DNA replication was significantly blocked. A clonal growth assay also confirmed a marked repression of cell growth. In a lung cancer xenograft node mice model, combination of EGCG and curcumin exhibited protective effect against weight loss due to tumor burden. Tumor growth was strongly repressed by the combination of the two agents, without causing any serious side-effect. Overall, these results strongly suggest that EGCG in combination with curcumin could be a candidate for chemoprevention agent of NSCLC.

摘要

(-)-表没食子儿茶素没食子酸酯(EGCG)和姜黄素是两种在全球范围内受到广泛研究的天然衍生物质。它们在多种癌症类型中展现出抗肿瘤作用。在本研究中,对这两种物质联合使用对非小细胞肺癌(NSCLC)细胞的影响进行了研究。结果显示,在低浓度下,EGCG和姜黄素联合使用能强烈增强细胞周期阻滞。流式细胞术分析表明,细胞停滞在G1期和S/G2期。两种主要的细胞周期相关蛋白细胞周期蛋白D1和细胞周期蛋白B1在EGCG和姜黄素存在时受到显著抑制。EdU(5-乙炔基-2'-脱氧尿苷)荧光染色显示DNA复制被显著阻断。克隆生长试验也证实细胞生长受到明显抑制。在肺癌异种移植瘤小鼠模型中,EGCG和姜黄素联合使用对因肿瘤负荷导致的体重减轻具有保护作用。两种物质联合使用能强烈抑制肿瘤生长,且未引起任何严重副作用。总体而言,这些结果有力地表明,EGCG与姜黄素联合使用可能是NSCLC化学预防剂的一个候选物。

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