茶硝香酰胺对高转移性Lewis肺癌细胞侵袭和转移的抑制作用  

Inhibitory Effects of TNC Against Invasion and Metastasis of Highly-Metastatic Lewis Lung Cancer

作　　者：盖静 刘真真[1] 朱荣芹 李筝 郑晓慧 闫春燕 杨美玲 刘昆[1] 张国营[1] GE Jing;LIU Zhen-zhen;ZHU Rong-qin;LI Zheng;ZHENG Xiao-hui;YAN Chun-yan;YANG Mei-ling;LIU Kun;ZHANG Guo-ying(Laboratory of Molecular Pharmacology,School of Pharmacy,Yantai University,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Yantai Uni)

机构地区：[1]烟台大学药学院分子药理学实验室,烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室(烟台大学),山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2018年第2期145-152,共8页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2015HM004)

摘　　要：本文旨在从动物体内外、细胞和分子水平上研究探讨茶硝香酰胺(TNC)对高侵袭和高转移性Lewis肺癌(LLC)细胞系侵袭和转移能力的影响.使用Transwell法观察TNC对LLC细胞侵袭能力的抑制作用;建立肿瘤转移动物模型,评估TNC对小鼠LLC细胞肺癌转移的抑制效果;以Western Blotting为检测手段,分析TNC对LLC细胞中相关蛋白表达的影响.实验结果表明,TNC药物浓度与LLC细胞侵袭和转移能力受到的抑制效果成正相关,抑制效果随浓度增大而增强;TNC能下调VEGFR1、VEGFR2、AKT、磷酸化AKT(p AKT)、RELA和MMP9蛋白的表达,并能上调E-cadherin蛋白的表达.分析实验结果可知,TNC能够明显抑制LLC细胞的侵袭,对小鼠体内LLC肺癌的转移同样有显著的抑制作用,从分子水平上,其作用机制与VEGFR介导的AKT/NF-κB信号传导通路有关,TNC有成为抑制高侵袭和高转移肺癌临床治疗药物或者辅助治疗药物的潜力.This study aims to explore the inhibitory effects of TNC against the invasion and metastasis of highly invasive and metastatic Lewis lung cancer(LLC)cell line at in vitro and in vivo as well as cellular and molecular levels.The transwell chamber assay is utilized to observe the effect of TNC on the invasion ability of LLC cells.An animal metastatic tumor model is established to evaluate the inhibitory effect of TNC on lung cancer metastasis in mice inoculated with LLC cells.The effects of TNC on the related protein expression in LLC cells are examined using Western Blotting.Transwell chamber and animal experiments show that the inhibitory effects on the invasion and metastasis of LLC cells are enhanced with the increase of TNC concentrations.TNC remarkably reduces the protein expressions of VEGFR1,VEGFR2,pAKT/AKT,RELA and MMP9 and markedly enhances the protein expression of E-cadherin in LLC cells.TNC can effectively inhibit the invasion of the highly invasive LLC cells and the metastasis of lung cancer in mouce.The molecular mechanisms of TNC action are involved in the VEGFR-mediated AKT/NF-κB signaling pathway.The present results suggest that TNC may have the potential to be a therapeutic and/or adjuvant therapeutic agent for highly metastatic lung cancer.

关 键 词：茶硝香酰胺 高转移肺癌 侵袭 转移 

分 类 号：TG376.2[金属学及工艺—金属压力加工]