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茶氨酸溴香酰胺对人宫颈癌细胞体内外生长的抑制作用
张华荣,季德鑫,刘欣,陈林林,孙富家,田绘绘,吴菲,刘昆,张国营
0
(烟台大学药学院分子药理学实验室,烟台 264005)
摘要:
将茶氨酸为母体合成的茶氨酸衍生物茶氨酸溴香酰胺(TBrC)与茶氨酸作比较,评估茶氨酸溴香酰胺对人宫颈癌细胞体内外生长的抑制作用与其分子机制。应用MTT等方法检测不同浓度的TBrC对人宫颈癌细胞体外生长的影响,运用蛋白质印迹法检测解析这些人宫颈癌细胞中与凋亡和生长密切相关蛋白的表达和药物可能的作用靶点。此外,通过建立动物肿瘤模型,评价TBrC对荷瘤裸鼠人宫颈癌生长的抑制效果。实验结果显示,TBrC抑制人宫颈癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对小鼠生长无明显毒性;TBrC作用的分子机制之一可能与抑制VEGFR1-Bcl-2/Bax信号传导通路相关。研究结果提示, TBrC具有广泛应用于临床治疗和(或)辅助治疗人宫颈癌和其他癌症的潜力。
关键词:  茶氨酸溴香酰胺  人宫颈癌  体内外生长抑制  药物靶点
DOI:
投稿时间:2013-10-07
基金项目:国家科技部十二五“863”项目(2012AA020206), 国家自然科学基金面上项目(30973553), 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 TBrC against in vitro and in vivo growth of human cervical cancer cells
ZHANG Huarong,JI Dexin,LIU Xin,CHEN Linlin,SUN Fujia,TIAN Huihui,WU Fei,LIU Kun,ZHANG Guoying
(Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, Yantai 264003)
Abstract:
The aim of this study is to investigate the inhibitory effects of TBrC, a synthesized theanine derivative on the growth of human cervical cancer cells and the molecular mechanisms of action both in vitro and in vivo. MTT assay was used to evaluate the effects of TBrC on the in vitro growth of human cervical cancer cells. Western blotting was employed to analyze the protein expressions and the possible targets of action related to the growth inhibition and apoptosis in the human cervical cancer cells treated with TBrC. In addition, an animal tumor mode was established to assess the inhibitory effects of TBrC on human cervical tumor growth in tumor-bearing mice. The experimental results showed that TBrC enhanced the growth inhibition of the human cervical cancer cells and human cervical tumor by multifold as compared with its parental compound (theanine) without detectable toxicity to the mice. All these results suggest that TBrC may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human cervical cancer and other cancers.
Key words:  TBrC  cervical cancer  growth inhibition in vitro & in vivo  drug targets

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