蛇床子素联合肿瘤坏死因子诱导凋亡配体对乳腺癌干细胞的杀伤效应

被引：10

作者：

王倩

郑海雅

周颖

钟益芳

机构：

[1] 丽水市人民医院

来源：

中国现代应用药学 | 2017年 / 02期

关键词：

蛇床子素; 肿瘤坏死因子诱导凋亡配体; 乳腺癌干细胞; Apaf-1; caspase-9; 凋亡;

D O I：

暂无

中图分类号：

R737.9 [乳腺肿瘤];

学科分类号：

100214 [肿瘤学];

摘要：

目的探讨蛇床子素联合肿瘤坏死因子诱导凋亡配体[tumor necrosis factor(TNF)-related apoptosis inducing ligand,TRAIL]对乳腺癌干细胞的杀伤效应及机制。方法用TRAIL及蛇床子素体外处理MCF-7乳腺癌非干细胞及MCF-7乳腺癌干细胞,MTT法检测乳腺癌细胞的细胞活力;流式细胞术检测乳腺癌细胞的凋亡;Western blot试验检测caspase-9和caspase-3的活化,凋亡酶激活因子(apoptotic protease activating facter-1,Apaf-1)的表达水平,细胞色素C的释放;免疫共沉淀法检测Apaf-1和caspase-9前体的相互作用。结果 MCF-7肿瘤干细胞对TRAIL的敏感性显著低于MCF-7非干细胞。在MCF-7肿瘤干细胞的培养体系中加入蛇床子素能显著提高TRAIL对MCF-7肿瘤干细胞的细胞活力抑制率。Western blot实验结果表明,蛇床子素能显著上调MCF-7肿瘤干细胞中Apaf-1的表达水平,但不影响细胞色素C的释放。在MCF-7肿瘤干细胞中转染Apaf-1 si RNA后,蛇床子素联合TRAIL对MCF-7肿瘤干细胞的协同杀伤活性受到显著抑制。另外,免疫共沉淀实验结果表明,蛇床子素联合TRAIL能显著诱导MCF-7肿瘤干细胞中Apaf-1与caspase-9前体的相互作用,并使之发生活化。结论蛇床子素通过上调Apaf-1的表达促进TRAIL对乳腺癌干细胞caspase-9的活化,从而增强TRAIL对乳腺癌干细胞的凋亡诱导效应。

引用

页码：225 / 231

页数：7

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