Combretastatin A-4氨基糖类衍生物CPU-XT-008抑制血管内皮细胞增殖的分子机制  被引量:1

Molecular mechanisms of combretastatin A-4 amino sugar derivative CPUXT-008 on inhibiting proliferation of vascular endothelial cells

在线阅读下载全文

作  者:何书英[1] 熊蕊[1] 刘坤[2] 徐云根[2] 

机构地区:[1]中国药科大学生命科学与技术学院,南京210009 [2]中国药科大学药物化学教研室,南京210009

出  处:《中国药科大学学报》2015年第5期594-599,共6页Journal of China Pharmaceutical University

基  金:江苏省自然科学基金资助项目(No.BK2010436)~~

摘  要:以人脐静脉内皮细胞(HUVEC)为模拟肿瘤血管内皮细胞的实验模型,研究combretastatin A-4(CA-4)的氨基糖类衍生物CPU-XT-008对HUVEC的增殖、周期分布、微管蛋白聚合以及关键周期调控蛋白表达的影响。采用MTT法检测CPU-XT-008对HUVEC增殖的影响;采用流式细胞仪检测CPU-XT-008对HUVEC周期分布的影响;采用免疫荧光染色检测CPU-XT-008对HUVEC凋亡及β-tubulin微管蛋白的聚合变化;采用Western blot检测CPU-XT-008对周期蛋白Cyclin B1,Cdc2和微管蛋白β-tubulin的影响。结果表明,CPU-XT-008能以微管蛋白为靶点抑制β-tubulin微管蛋白聚合,通过上调HUVEC的细胞周期蛋白Cyclin B1水平表达,下调细胞周期依赖性激酶Cdc2蛋白水平的表达从而引发细胞G2/M期阻滞,抑制细胞增殖并诱导细胞凋亡。Taking human umbilical vein endothelial cells (HUVEC)as experimental model which can simulate tumor-derived vascular endothelial cells;the effects of CPU-XT-008;an amino sugar derivative of combretastatin A-4 (CA-4);on HUVEC proliferation;cell cycle distribution;tubulin polymerization and the key regulatory pro-tein of cell cycle were studied.The effect of CPU-XT-008 on the proliferation of HUVEC was determined by MTT assay.The cell cycle distribution caused by CPU-XT-008 was detected by flow cytometry.Immunofluorescence was used to detect apoptosis and tubulin polymerization.The expressions of Cyclin B1;Cdc2 and β-tubulin were detected by Western blotting.Results demonstrated that CPU-XT-008 could target tubulin and inhibit the poly-merization ofβ-tubulin;and it could lead to G2/M cell cycle arrest in HUVEC by up-regulating Cyclin B1 expres-sion and down-regulating Cdc2 and p-Cdc2 expression;which resulted in inhibiting the proliferation of HUVEC and inducing its apoptosis.

关 键 词:COMBRETASTATIN A-4 CPU-XT-008 氨基糖类衍生物 人脐静脉内皮细胞 微管蛋白 细胞周期 

分 类 号:R96[医药卫生—药理学]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象