茶氨酸溴香酰胺对肺癌细胞生长的影响与其作用分子机制的研究  

Inhibitory effects of TBrC against the growth of lung cancer cells and the molecular mechanisms of action

作　　者：陈林林[1] 季德鑫[1] 刘欣[1] 张华荣[1] 孙富家[1] 刘昆[1] 姚建文[1] 张国营[1] 

机构地区：[1]烟台大学药学院分子药理学实验室,烟台264005

出　　处：《安徽农业大学学报》2013年第2期242-249,共8页Journal of Anhui Agricultural University

基　　金：国家科技部十二五"863"课题(2012AA020206);国家自然科学基金面上项目(30973553);山东省科技攻关项目(2009GG10002087);山东省自然科学基金项目(ZR2012HM016)共同资助

摘　　要：以茶氨酸作为对照,评估现已合成的茶氨酸衍生物茶氨酸溴香酰胺(TBrC)对肺癌细胞生长的抑制作用与其分子机制。采用苔芬兰染色等方法检测不同浓度的TBrC对肺癌细胞和正常细胞生长的影响,运用Hoechst33258荧光染色观察分析有关活性成分对肺癌细胞凋亡的诱导作用,应用蛋白质印迹法检测解析这些肺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对荷瘤小鼠肺癌生长的抑制效果。实验结果显示,TBrC抑制肺癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对正常细胞和小鼠生长无明显毒性;TBrC显示了诱导肺癌细胞凋亡的作用,其分子机制可能与抑制VEGFR1-Akt-NF-κB信号传导通路相关。本研究结果提示,TBrC具有广泛应用于临床治疗和(或)辅助治疗高转移肺癌和其他癌症的潜力。The purpose of this study is to investigate the inhibitory effects of TBrC,a synthesized theanine derivative on the growth of lung cancer cells and the molecular mechanisms of action.Trypan blue staining and other assays were used to evaluate the effects of TBrC on the growth of normal cells and lung cancer cells.Hoechst 33258 staining was adapted to examine the apoptosis in the lung cancer cells treated with TBrC.Western blotting was employed to analyze the protein expressions and the possible targets of action related to the growth inhibition and apoptosis in the lung cancer cells treated with TBrC.In addition,an animal tumor mode was established to assess the inhibitory effects of TBrC on lung tumor growth in tumor-bearing mice.The experimental results show that TBrC has enhanced the growth inhibition of the lung cancer cells and lung tumor by multifold as compared with theanine without detectable toxicity to the normal cells and mice.TBrC induces the apoptosis in the lung cancer cells.All these results suggest that TBrC may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of highly-metastatic lung cancer and other cancers.

关 键 词：茶氨酸溴香酰胺 肺癌 体内外生长抑制 凋亡 

分 类 号：R979.1[医药卫生—药品] TS272[医药卫生—药学]