茶硝香酰胺联合吉非替尼对人非小细胞肺癌迁移的影响  

Effects of TNC and Gefitinib on Cell Migration of Human Non-Small Cell Lung Cancer

作　　者：石晓玉 张燕 孙彦莉 盖静 刘昆[1] 张国营[1] SHI Xiao-yu;ZHANG Yan;SUN Yan-li;GE Jing;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 University,Yantai 264005,China)

机构地区：[1]烟台大学药学院分子药理实验室,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）》2020年第4期409-417,478,共10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(ZR2019MH070).

摘　　要：本实验旨在探究茶氨酸衍生物茶硝香酰胺(TNC)和吉非替尼联合是否增强吉非替尼对人非小细胞肺癌A549细胞迁移的影响与其可能作用的分子机制,为抑制肺癌远处转移和减少吉非替尼毒副作用提供新思路.采用细胞划痕术检测联合用药前后细胞迁移能力变化;上皮-间质转化(EMT)诱导实验结合Transwell实验观察发生EMT后A549迁移能力改变;蛋白免疫印迹法检测相关蛋白的表达.结果显示:TNC联合吉非替尼可显著抑制A549细胞迁移,且间质标志物N-Cadherin、Vimentin显著下调,上皮细胞标志物E-Cadherin明显上调,与迁移相关转录抑制因子ZEB、Slug、Snail、Twist表达显著下降,同时AKT、NF-κB等蛋白表达水平下调.提示TNC联合吉非替尼可能是通过抑制A549细胞的EMT过程从而增强吉非替尼对A549细胞迁移的抑制作用.We present an experimental study to explore whether the combination of theanine derivative(TNC)and gefitinib can enhance the repressive effects of gefitinib on the migration of human non-small cell lung adenocarcinoma A549 cells,and provide proofs for inhibiting distant metastasis of lung cancer and reducing the side effects of gefitinib.The wound healing assay is used to examine changes in the cell migration before and after the combination treatments.Epithelial-mesenchymal transition(EMT)induction experiments combined with the transwell chamber assay are used to observe the effects of combined treatment on the migration ability of A549 after EMT occurring.Western blotting is used to detect the expressions of related proteins.The results show that TNC and gefitinib significantly inhibits the migration of A549 cells,the interstitial markers N-cadherin and Vimentin are significantly down-regulated,and the expression of epithelial marker E-Cadherin is up-regulated.Migration-related transcription inhibitors ZEB,Slug,Twist and Snail are also significantly down-regulated.The protein expressions of AKT,NF-κB,EGF,HGF,c-MET,and K-Ras are significantly decreased.Our research suggests that TNC in combination with gefitinib may enhance the inhibitory effects of gefitinib on A549 cell migration by suppressing the process of EMT.

关 键 词：茶硝香酰胺 吉非替尼 联合用药 迁移 上皮-间质转化(EMT) 抑制作用 

分 类 号：R96[医药卫生—药理学]