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茶氨酸衍生物茶溴香酰胺脂质体对人肺癌细胞 生长和迁移的抑制作用
引用本文:闫春燕,刘辉,朱荣芹,刘真真,李筝,孙考祥,杨美玲,盖静,郑晓慧,吴犇昊,张国营. 茶氨酸衍生物茶溴香酰胺脂质体对人肺癌细胞 生长和迁移的抑制作用[J]. 安徽农业大学学报, 2018, 45(1): 15-24. DOI: 10.13610/j.cnki.1672-352x.20180302.023
作者姓名:闫春燕  刘辉  朱荣芹  刘真真  李筝  孙考祥  杨美玲  盖静  郑晓慧  吴犇昊  张国营
作者单位: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),烟台264005;烟台市毓璜顶医院药学部,烟台,264001;山东营东颖昊生物科技有限公司,烟台,264670
基金项目:国家科技部十二五“863”项目,十三五国家重点研发计划项目,山东省自然科学基金项目
摘    要:为了探索研究茶氨酸衍生物茶溴香酰胺制备的脂质体(TBrC-L)对人非小细胞肺癌A549细胞生长和迁移的抑制作用与其分子机制,采用薄膜分散法制备了TBrC-L,通过MTT法检测不同浓度的TBrC-L对人肺癌A549细胞生长的抑制作用;使用流式细胞术检测TBrC-L对人肺癌A549细胞凋亡的诱导作用;利用Transwell chamber法观察TBrC-L对人肺癌A549细胞迁移作用的影响;应用蛋白质印迹法检测人肺癌A549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。实验结果显示,TBrC-L对人肺癌A549细胞生长和迁移有显著的抑制作用,促进肿瘤细胞凋亡、抑制肿瘤细胞生长和迁移可能是其抗人肺癌作用的重要机制,其作用的分子机制涉及到抑制EGFR、VEGFR1、VEGFR~2和Met受体介导的Akt和NF-κB信号传导通路,本研究结果提示,TBrC-L具有应用于临床治疗和(或)辅助治疗人肺癌的潜力。

关 键 词:茶溴香酰胺脂质体  人肺癌  生长和迁移  抑制作用机制

Inhibitory effects of theanine derivative TBrC-prepared liposome on the growth and migration of human lung cancer cells
YAN Chunyan,LIU Hui,ZHU Rongqin,LIU Zhenzhen,LI Zheng,SUN Kaoxiang,YANG Meiling,GE Jing,ZHENG Xiaohui,WU Benhao and ZHANG Guoying. Inhibitory effects of theanine derivative TBrC-prepared liposome on the growth and migration of human lung cancer cells[J]. Journal of Anhui Agricultural University, 2018, 45(1): 15-24. DOI: 10.13610/j.cnki.1672-352x.20180302.023
Authors:YAN Chunyan  LIU Hui  ZHU Rongqin  LIU Zhenzhen  LI Zheng  SUN Kaoxiang  YANG Meiling  GE Jing  ZHENG Xiaohui  WU Benhao  ZHANG Guoying
Affiliation: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 University, Yantai 264005,Department of Pharmacy,Yuhuangding Hospital of Yantai, Yantai 264001,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005,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 University, Yantai 264005 and 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 University, Yantai 264005
Abstract:This study is to investigate the inhibitory effects of theanine derivative TBrC-prepared liposome (TBrC-L) on the growth and migration of human non-small-cell lung cancer (NSCLC) A549 cells and its molecular mechanism.The MTT assay and flow cytometry were used to detect the effects of different concentrations of TBrC-L on the growth and apoptosis of human lung cancer A549 cells,respectively.The transwell chamber assay and westem blot were applied to determining the effects of TBrC-L on the cancer cell migration and related protein expressions,respectively.The results showed that TBrC-L significantly inhibited the cancer cell growth and migration and induced apoptosis in human lung cancer A549 cells.The suppression of the cancer cell growth and migration as well as the induction of apoptosis may be the important anticancer activities of TBrC-L against the human lung cancer A549 cells.The molecular mechanism of TBrC-L action may be involved in restraining the EGFR-,VEGFR1-,VEGFR2-and Met-mediated signaling transduction pathways of Akt and NF-κB in the human cancer cells.The results suggested that TBrC-L may have the potential to be used in clinical treatment and/or adjuvant treatment of human non-small-cell lung cancer.
Keywords:TBrC-L   human lung cancer   growth and migration   mechanisms of inhibition
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