首页|藁本内酯对胃癌细胞增殖、凋亡和血管生成的影响及其作用机制

藁本内酯对胃癌细胞增殖、凋亡和血管生成的影响及其作用机制

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目的 探讨藁本内酯对胃癌细胞增殖、凋亡和血管生成的影响及其作用机制.方法 培养人胃癌细胞NCI-N87,细胞计数试剂盒-8(CCK-8)法检测不同浓度Ligustilide对NCI-N87细胞存活率的影响;根据实验要求将细胞分为对照组,藁本内酯低、中、高浓度组(藁本内酯-L、M、H组),藁本内酯-H+DMOG(HIF-1α激活剂)组;采用EDU实验检测各组NCI-N87细胞增殖能力;流式细胞术检测各组NCI-N87细胞凋亡;酶联免疫吸附法(ELISA)检测各组NCI-N87细胞分泌血管内皮生长因子A(VEGFA)水平;体外管形成实验检测各组细胞血管生成情况;蛋白免疫印迹(Western blot)检测各组NCI-N87细胞缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、细胞增殖核抗原(Ki67)、裂解的半胱天冬酶-3(cleaved-Caspase3)、半胱天冬酶-3(Caspase3)蛋白表达.结果 与对照组相比,藁本内酯-L、M、H组NCI-N87细胞增殖能力、培养液中VEGFA水平、血管生成能力、细胞HIF-1α、VEGF、Ki67蛋白表达显著降低,细胞凋亡率以及cleaved-Caspase3/Caspase3蛋白表达显著升高,且存在浓度依赖性(P<0.05);与藁本内酯-H组相比,藁本内酯-H+DMOG组可部分逆转藁本内酯-H组对NCI-N87细胞行为及以上蛋白表达的影响(P<0.05).结论 藁本内酯可通过调节HIF-1α/VEGF信号通路抑制胃癌细胞增殖、血管生成,并诱导其凋亡.
Effect and mechanism of ligustilide on the proliferation,apoptosis and angiogenesis of gastric cancer cells
Objective To investigate the effect and mechanism of Ligustilide on the proliferation,apoptosis and angiogenesis of gastric cancer cells.Methods Human gastric cancer cells NCI-N87 were cultured,and the effect of Ligustilide on the survival of NCI-N87 cells was detected by cell counting Kit 8(CCK-8).The cells were divided into the control group,low,medium and high doses of Ligustilide groups(Ligustilide-L,M and H groups),and Ligustilide-H+DMOG(HIF-1α activator)group.The proliferation of NCI-N87 cells was detected by EDU assay.The apoptosis of NCI-N87 cells was detected by flow cytometry.The level of vascular endothelial growth factor A(VEGFA)secreted by NCI-N87 cells was detected by enzyme-linked immunosorbent assay(ELISA).Angiogenesis of cells was detected by tube formation in vitro.Western blot was applied to detect the expression of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),cell proliferation-associated nuclear antigen(Ki67),cleaved caspase-3,and caspase-3 in NCI-N87 cells.Results Compared with the control group,the proliferation,VEGFA level,angiogenesis,and the expression of HIF-1α,VEGF and Ki67 in NCI-N87 cells were significantly decreased in the Ligustilide-L,M and H groups,but the cell apoptosis rate and cleaved-Caspase3/Caspase3 expression were significantly increased in a concentration-dependent manner(P<0.05).Compared with Ligustilide-H group,Ligustilide-H+DMOG group partially reversed the effect of Ligustilide-H group on the behavior and above protein expression of NCI-N87 cells(P<0.05).Conclusion Ligustilide can inhibit the proliferation and angiogenesis,and induce apoptosis of gastric cancer cells by regulating the HIF-1α/VEGF pathway.

LigustilideHIF-1α/VEGF signaling pathwaygastric cancerproliferationapoptosisangiogenesis

陈莎、吴健瑜、谭汉添

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广州中医药大学第一附属医院药学部,广东广州 510405

广州中医药大学第一附属医院普外科,广东广州 510405

藁本内酯 HIF-1α/VEGF信号通路 胃癌 增殖 凋亡 血管生成

广东省中医药局科研项目

202305042253436670

2024

广东药科大学学报
广东药学院

广东药科大学学报

CSTPCD
影响因子:0.698
ISSN:1006-8783
年,卷(期):2024.40(2)
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