银杏叶总黄酮通过抑制c-Met介导的上皮-间充质转化对人肺癌细胞迁移和侵袭的影响  

Effects of Total Flavone in Ginkgo Biloba Leaves on the Migration and Invasion of Human Lung Cancer Cells by Inhibiting c-Met-mediated Epithelial-mesenchymal Transformation

作　　者：杨谦 张军 杜少杰 谭雪敏[1] 马玉泉[1] Yang Qian;Zhang Jun;Du Shaojie;Tan Xuemin;Ma Yuquan(Department of Thoracic Surgery,Handan Central Hospital,Hebei Handan 056001,China;Department of Anesthesiology,Handan Central Hospital)

机构地区：[1]邯郸市中心医院胸外二科,河北邯郸056001 [2]邯郸市中心医院麻醉科

出　　处：《中国药师》2020年第9期1710-1714,共5页China Pharmacist

基　　金：河北省医学科学研究重点课题计划项目(编号:20180717)。

摘　　要：目的:探讨银杏叶总黄酮通过抑制肝细胞生长因子受体(c-Met)介导的上皮-间充质转化对人肺癌细胞迁移和侵袭的影响。方法:体外培养A549细胞进行实验,采用细胞计数试剂盒8(CCK-8)法确定银杏叶总黄酮对A549细胞的半数抑制浓度,对照组加入无血清RPMI-1640培养基,银杏叶总黄酮低、中、高剂量组加入终浓度为50,100,200μg·ml^-1的银杏叶总黄酮,顺铂组给予终浓度为5μg·ml^-1的顺铂,继续培养24 h后检测细胞迁移和侵袭能力,同时检测A549细胞内肝细胞生长因子(HGF)、c-Met、磷酸化c-Met(p-c-Met)、上皮型钙黏蛋白(E-cadherin)和抗波形蛋白(Vimentin)表达水平。结果:随着银杏叶总黄酮浓度增加,A549细胞增殖率降低,与对照组比较,差异有统计学意义(P<0.05)。当银杏叶总黄酮浓度为200μg·ml^-1时,抑制率为52.45%,故选200μg·m^l-1作为半数抑制浓度;各剂量组A549细胞内c-Met水平变化不显著,差异无统计学意义(P>0.05);与对照组相比,各银杏叶总黄酮组和顺铂组A549细胞迁移能力、细胞侵袭数、HGF、p-c-Met、Vimentin水平降低,E-cadherin水平增加,差异有统计学意义(P<0.05),各银杏叶总黄酮组之间呈剂量依赖性,但效果不如顺铂组,差异有统计学意义(P<0.05)。结论:银杏叶总黄酮通过下调c-Met信号,有效抑制A549细胞的上皮-间充质转化,从而发挥抗迁移和侵袭作用,该发现可能为肺癌的治疗提供新的思路。Objective:To investigate the effect of total flavone in Ginkgo biloba leaves on the migration and invasion of human lung cancer cells by inhibiting Hepatocyte growth factor receptor(c-Met)-mediated epithelial-mesenchymal transformation.Methods:A549 cells were cultured in vitro.Cell count kit 8(CCK-8)method was used to determine the half inhibitory concentration of total flavone in Ginkgo biloba leaves on A549 cells.RPMI-1640 medium without serum was added to the control group,50,100 and 200μg·ml-1 total flavone in Ginkgo biloba leaves was respectively added to the low,middle and high dose groups,and 5μg·ml^-1 cisplatin was added to cisplatin group.The cell migration and the expression levels of hepatocyte growth factor(HGF),c-Met,phosphorylation c-Met(p-c-Met),E-cadherin and vimentin in A549 cells were measured.Results:The proliferation rate of A549 cells was decreased with the increase of total flavone concentration,and compared with the control group,the difference was statistically significant(P<0.05).When the concentration of propofol was 200μg·ml^-1,the inhibition rate was 52.45%,therefore,200μg·ml^-1 was selected as the half inhibition concentration.The level of c-Met in A549 cells of each dose group did not change significantly(P>0.05).Compared with those in the control group,the level of A549 cells migration ability,cell invasion number,HGF,p-c-Met and vimentin were significantly decreased,and the levels of E-cadherin in total flavone in Ginkgo biloba leaves groups and cisplatin group were significantly increased,and the differences were statistically significant(P<0.05),and the dose-dependent manner was significant among total flavone in Ginkgo biloba leaves groups(P<0.05),while the effect was not as good as that of cisplatin group,and the difference was statistically significant(P<0.05).Conclusion:Total flavone in Ginkgo biloba leaves can effectively inhibit the epithelial mesenchymal transition of A549 cells by down-regulating the c-Met signal,so as to play the role of anti-migration and invasi

关 键 词：银杏叶总黄酮 肝细胞生长因子受体 上皮-间充质转化 肺癌 细胞迁移 细胞侵袭 

分 类 号：R965.1[医药卫生—药理学]