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硼替佐米抑制PI3K/Akt通路增强胃癌细胞对TRAIL诱导凋亡的敏感性
引用本文:刘静,徐玲,刘云鹏,曲秀娟,张晔,侯科佐,胡雪君,姜又红.硼替佐米抑制PI3K/Akt通路增强胃癌细胞对TRAIL诱导凋亡的敏感性[J].世界华人消化杂志,2010,18(18).
作者姓名:刘静  徐玲  刘云鹏  曲秀娟  张晔  侯科佐  胡雪君  姜又红
作者单位:1. 中国医科大学附属第一医院肿瘤内科,辽宁省沈阳市,110001
2. 中国医科大学附属第一医院呼吸科,辽宁省沈阳市,110001
3. 中国医科大学附属第一医院肿瘤研究所第二研究室,辽宁省沈阳市,110001
基金项目:国家自然科学基金资助项目
摘    要:目的:研究硼替佐米对TRAIL诱导胃癌细胞凋亡的影响, 探讨PI3K/Akt通路在TRAIL诱导凋亡中的作用.方法:不同浓度的TRAIL和/或硼替佐米作用于人胃癌细胞系MGC803细胞, MTT法检测细胞存活率, 流式细胞术PI染色检测细胞凋亡.Western blot法检测caspase裂解及p-Akt表达水平的变化.结果:50 nmol/L硼替佐米预处理细胞2 h, 之后予100 μg/L TRAIL继续作用24 h, 细胞存活率明显低于TRAIL单独处理组(35.1%±2.7% vs71.0%±4.3%, P <0.01); 细胞凋亡率明显高于TRAIL单药组(31.3%±2.0% vs 8.2%±0.8%,P <0.01). 20 nmol/L硼替佐米预处理未能增强细胞对TRAIL的敏感性. 进一步研究发现,TRAIL可活化PI3K/Akt通路, 硼替佐米预处理可阻止PI3K/Akt通路的活化, 进而增强细胞对TRAIL诱导凋亡的敏感性.结论:硼替佐米通过抑制TRAIL诱导的PI3K/Ak t通路活化, 增强胃癌MGC803细胞对TRAIL诱导凋亡的敏感性.

关 键 词:肿瘤坏死因子相关凋亡诱导配体  硼替佐米  胃癌  凋亡

Bortezomib enhances the sensitivity of gastric cancer cells to TRAIL-induced apoptosis by inhibiting the PI3K/Akt pathway
Jing Liu,Ling Xu,Yun-Peng Liu,Xiu-Juan Qu,Ye Zhang,Ke-Zuo Hou,Xue-Jun Hu,You-Hong Jiang.Bortezomib enhances the sensitivity of gastric cancer cells to TRAIL-induced apoptosis by inhibiting the PI3K/Akt pathway[J].World Chinese Journal of Digestology,2010,18(18).
Authors:Jing Liu  Ling Xu  Yun-Peng Liu  Xiu-Juan Qu  Ye Zhang  Ke-Zuo Hou  Xue-Jun Hu  You-Hong Jiang
Institution:Jing Liu,Ling Xu,Yun-Peng Liu,Xiu-Juan Qu,Ye Zhang,Ke-Zuo Hou,Department of Medical Oncology,the First Hospital of China Medical University,Shenyang 110001,Liaoning Province,China Xue-Jun Hu,Department of Respiratory Diseases,China You-Hong Jiang,Cancer Research Institute,China
Abstract:AIM:To investigate the effect of bortezomib on TRAIL-induced apoptosis in human gastric cancer cells, and to elucidate the role of the phosphoinositide 3-kinases (PI3K)/Akt signaling pathway in TRAIL-induced apoptosis of gastric cancer cells.METHODS:Human gastric cancer MGC803 cells were cultured and treated with TRAIL and/or bortezomib.Cell viability was determined by MTT assay.Apoptosis was detected by flow cytometry.Caspase cleavage and the level of phosphor-Akt were determined by Western blot.RESULTS:Ce...
Keywords:PI3K/Akt
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