[Inhibitory effect of andrographolide on angiogenesis induced by the supernatant from cultured tumor cells]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Aug 28;43(8):821-825. doi: 10.11817/j.issn.1672-7347.2018.08.001.
[Article in Chinese]

Abstract

To determine the effect of andrographolide (Andro) on angiogenesis of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with different concentrations of Andro and the cell viability was detected with Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of Andro. Matrigel was used to make capillary formation of HUVECs and the effect of Andro on capillary formation was evaluated by calculating the percentage of capillary formation. Moreover, the effects of Andro and the supernatant from cultured A549 tumor cells on capillary formation were evaluated by calculating the percentage of capillary formation. The effect of Andro on the expression of matrix metalloproteinase-9 (MMP-9) was determined with Western blot. Results: The cell viability of HUVECs decreased with the increase of Andro concentrations. IC50 was 20 μmol/L. The capillary formation of HUVECs was inhibited when treated with 20 μmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the promotion of the capillary formation induced by the supernatant from cultured tumor cells. Andro could suppress the expression of MMP-9 and antagonize the capillary formation. Conclusion: Andro inhibits the capillary formation of HUVECs and can antagonize the promotion of angiogenesis induced by the supernatant from cultured tumor cells.

目的:探讨穿心莲内酯(andrographolide,Andro)对人脐带静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)成管能力的影响。方法:将不同体积浓度的Andro溶液作用于HUVECs,采用细胞计数试剂盒-8(Cell Counting Kit-8,CCK-8)检测细胞存活率。采用半数致死量(IC50)的Andro溶液作用于HUVECs,采用Matrigel胶使HUVECs成管,通过计算成管率来评估Andro溶液对HUVECs成管能力的影响。此外,将A549细胞分泌物与Andro溶液同时处理HUVECs,检测其成管情况。采用Western印迹检测Andro溶液对基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达水平的影响。结果:Andro溶液可抑制HUVECs的增殖,且呈浓度依赖性;Andro溶液对HUVECs的IC50为20 μmol/L。选取20 μmol/L的Andro溶液作用于HUVECs 24 h,发现Andro溶液显著抑制HUVECs的成管能力。另外,A549细胞分泌物促进HUVECs成管作用,而Andro溶液拮抗肿瘤细胞分泌物对HUVECs成管的促进作用,降低MMP-9的表达。结论:Andro能够抑制HUVECs成管,而且能够拮抗肿瘤细胞分泌物对HUVECs成管的促进作用,从而抑制血管新生。.

MeSH terms

  • Capillaries / drug effects
  • Cell Survival
  • Collagen
  • Culture Media*
  • Diterpenes / pharmacology*
  • Drug Combinations
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • Laminin
  • Matrix Metalloproteinase 9 / metabolism
  • Neovascularization, Pathologic / enzymology
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / prevention & control*
  • Proteoglycans
  • Tumor Cells, Cultured

Substances

  • Culture Media
  • Diterpenes
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • andrographolide
  • Collagen
  • Matrix Metalloproteinase 9