阿司匹林抑制NF-κB对人卵巢癌TNF-α诱导细胞凋亡的增敏作用及机制研究
Study on the sensitization of TNF-α-induced apoptosis via inhibition of the NF-κB by Aspirin and its mechanism
作者:凌波;严亨秀;
Author:
收稿日期: 年卷(期)页码:2014,29(04):-374-377
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:卵巢癌;肿瘤坏死因子-α;阿司匹林;核因子-κB;增敏作用;作用机制;细胞凋亡
Key words:
基金项目:西南民族大学中央高校基本科研业务费专项基金项目资助(13NZYBS13)
中文摘要
目的考察以阿司匹林抑制肿瘤坏死因子-α(TNF-α)治疗中激活的核因子-κB(NF-κB)来增加卵巢癌对TNF-α的敏感性。方法将阿司匹林与TNF-α共处理卵巢癌细胞SKOV3后,用Western Blot检测细胞中磷酸化IκBα、COX-2、XIAP、cIAP-1/2的变化;用流式细胞术检测细胞的凋亡与活性氧(ROS)积累;Caspase与NF-κB的活性分别用Apo-ONETM均质Caspase-3/7检测系统与凝胶迁移滞后(EMSA)检测。结果阿司匹林和TNF-α联合治疗诱导SKOV3人卵巢癌细胞的凋亡显著大于两种药物单独用药。阿司匹林通过降解及阻止IκBα的磷酸化来抑制NF-κB的活化;阿司匹林/TNF-α联合治疗显著影响XIAP的水平,但不包括IAP家族的其他成员(cIAP1、cIAP2),表示该效果具有特异性;阿司匹林/TNF-α能诱导活性氧的产生;抗氧化剂的N-乙酰基-L-半胱氨酸则阻断XIAP下调与诱导的凋亡。结论阿司匹林/TNF-α诱导的细胞凋亡由活性氧依赖的XIAP下调介导。
参考文献
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