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茶氨酸和其衍生物茶氨酸氯香酰胺对高转移的 人乳腺癌细胞生长的抑制作用
吴菲,田绘绘,季德鑫,张华荣,刘真真,朱荣芹,刘昆,姚建文,张国营
0
(烟台大学药学院 分子药理学实验室,烟台 264005)
摘要:
旨在评估茶氨酸(T)和本实验室合成的新颖的茶氨酸衍生物-茶氨酸氯香酰胺(TClC)对高转移的人乳腺癌MDA-MB-231细胞生长的抑制作用,并对其作用的机制进行初步探究。采用MTT法检测不同浓度的T和TClC对MDA-MB-231细胞体外生长的影响,采用Western blotting对MDA-MB-231细胞中与癌细胞凋亡相关蛋白的表达以及药物作用可能的分子靶点进行检测。结果显示,随着浓度的增高,T和TClC对人乳腺癌MDA-MB-231细胞体外生长的抑制作用逐渐增强, TClC的抑制作用要明显强于T;T和TClC均能够下调抗凋亡蛋白Bcl-2的表达水平,同时上调促凋亡蛋白Bax的表达水平,使Bcl-2/Bax比率减少。此外,T和TClC均能抑制血管内皮生长因子受体VEGFR1和核转录因子NF-κB的表达, 而TClC的抑制作用要明显强于T。T和TClC对这些蛋白水平的调节作用可能是抑制MDA-MB-231细胞生长的重要机制之一。这些结果表明,T和TClC对治疗高转移的人乳腺癌可能具有广阔的应用前景。
关键词:  茶氨酸  茶氨酸氯香酰胺  高转移人乳腺癌  体外抑制
DOI:10.13610/j.cnki.1672-352x.20141029.020
投稿时间:2014-03-05
基金项目:国家科技部十二五“863”项目(2012AA020206), 山东省科技攻关项目(2009GG10002087)和山东省自然科学基 金项目(ZR2012HM016)共同资助。
Inhibitory effects of theanine and TClC on the growth of human breast cancer cells
WU Fei,TIAN Huihui,JI Dexin,ZHANG Huarong,LIU Zhenzhen,ZHU Rongqin,LIU Kun,YAO Jianwen,ZHANG Guoying
(Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, Yantai 264005)
Abstract:
This study was to assess the inhibitory effects of theanine (T) and TClC (a synthesized novel theanine derivative) on the growth of highly-metastasis human breast MDA-MB-231 cells and explore the mechanisms of such an inhibition. The MTT assay was used to evaluate the effects of different concentrations of T and TClC on the grown of in vitro MDA-MB-231 cells. Western blot analysis was employed to detect the expressions of apoptosis-related proteins and the possible targets of drug actions in the MDA-MB-231 cells. The experimental results showed that the inhibitory effects of T and TClC on the growth of MDA-MB-231 cells are gradually enhanced with the increase of the concentrations. TClC showed a much stronger inhibition of cell growth than T. T. TClC down-regulated the expression level of antiapoptotic Bcl-2 protein and up-regulated the expressions of proapoptotic Bax protein, leading to the reduction of Bcl-2/Bax ratio. In addition, T and TClC reduced the protein level of NF-κB and VEGFR1. TClC exhibited much stronger effects on regulating these proteins than T. The expression regulation of these proteins by TClC and T might be one of the important mechanisms of the cell growth suppression. All these findings suggested that T and TClC may have potential to the treatment of highly-metastasis human breast cancer.
Key words:  theanine  TClC  human breast cancer  growth inhibition in vitro

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