摘要
目的南蛇藤提取物(COE)对非小细胞肺癌血管生成的抑制作用及其可能的作用机制。方法体外培养A549细胞,将细胞分为对照组(Control,细胞培养液中不进行任何处理)、南蛇藤提取物组(培养液中添40 mg/kg COE)、Notch抑制剂(IMR-1)组(培养中加入50 mg/kg IMR-1)、COE+IMR-1组(细胞培养基中添加40 mg/kg与50mg/kg IMR-1)。CCK-8法检测细胞增殖活性;Transwell消失检测细胞侵袭、迁移能力;体外血管形成实验检测细胞血管生成能力;免疫印迹法检测Notch1、Jagged1、Hes1、血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)、碱性成纤维细胞生长因子2(bFGF2)蛋白表达。结果与Control组相比,COE组、IMR-1组细胞增殖率降低,细胞侵袭、迁移数量降低,Notch1、Jagged1、Hes1蛋白表达降低,环状血管结构数量减少,VEGF、bFGF2、MMP-9蛋白表达降低(P<0.05)。与COE组、IMR-1组相比,COE+IMR-1组细胞增殖率降低,细胞侵袭、迁移数量降低,Notch1、Jagged1、Hes1蛋白表达降低,环状血管结构数量减少,VEGF、bFGF2、MMP-9蛋白表达降低(P<0.05)。结论南蛇藤提取物能够抑制非小细胞肺癌A549细胞增殖、侵袭、迁移和血管形成,其可能是通过对Notch信号通路的抑制实现的。
Objective To study the inhibitory effect of Celastrus orbiculatus extract(COE)on angiogenesis of non-small cell lung cancer(NSCLC)and its possible mechanism. Methods A549 cells were cultured in vitro and divided into control group(without any treatment in cell culture medium),extract of Celastrus orbiculatus group(40 mg/kg COE added in culture medium),IMR-1 group(50 mg/kg IMR-1 added in culture medium),COE+IMR-1 group(40 mg/kg and 50 mg/kg IMR-1 added in cell culture medium). CCK-8 assay was used to detect cell proliferation activity. Transwell disappearance assay was used to detect cell invasion and migration abilities. In vitro angiogenesis assay was used to detect cell angiogenesis ability. Western blot was used to detect the protein expressions of Notch 1,Jagged 1,Hes 1,vascular endothelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9)and basic fibroblast growth factor 2(bFGF2). Results Compared with the control group,the proliferation rate of COE group and IMR-1 group decreased;the numbers of cell invasion and migration decreased;the expressions of Notch1,Jagged1 and Hes1 proteins decreased;the number of annular vascular structure decreased,and the expressions of VEGF,b FGF2 and MMP-9 proteins decreased(P<0.05). Compared with COE group and IMR-1 group,the proliferation rate of COE+IMR-1 group decreased;the numbers of cell invasion and migration decreased;the expressions of Notch1,Jagged1 and Hes1 proteins decreased,the number of annular vascular structure decreased,and the expressions of VEGF,b FGF2 and MMP-9 proteins decreased(P<0.05). Conclusion The extract of Celastrus orbiculatus could inhibit the proliferation,invasion,migration and angiogenesis of non-small cell lung cancer A549 cells,which might be achieved by inhibiting Notch signaling pathway.
作者
郜娜
杨庆宇
GAO Na;YANG Qing⁃yu(Department of Pharmacy,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou,Henan 450008;Zhengzhou People's Hospital,Ministry of Pharmacy,Zhengzhou,Henan 450000,China)
出处
《热带医学杂志》
CAS
2020年第3期341-345,F0003,共6页
Journal of Tropical Medicine
基金
国家自然科学基金(81703759)
河南省医药卫生科研项目(201303188)。
关键词
南蛇藤
非小细胞肺癌
NOTCH通路
Celastrus orbiculatus
Non-small cell lung cancer
Notch pathway
