siRNA沉默Twist1增强吉西他滨诱导胰腺癌细胞凋亡的研究
Study on the Twist1 silencing by small interfering RNA enhanced Gemcitabine-induced cell death in pancreatic cancer cells
作者：邢人鑫;冯敏;
Author：
收稿日期： 年卷（期）页码：2015,30(02):-192-195
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：胰腺癌;Twist1;吉西他滨;线粒体;增敏;小干扰RNA;辣根过氧化酶;细胞调亡;基因表达;Twist1沉默
Key words：
基金项目：
中文摘要
目的通过抑制Twist1来观察胰腺癌细胞对吉西他滨化疗敏感性的变化。方法通过靶向人Twist1基因小干扰RNA(siRNA)抑制Twist1的表达;用Western法检测Twist1的表达、Annexin V/PI染色和流式细胞术检测吉西他滨诱导的细胞凋亡;通过Western blot检测caspase及可能的丝裂原活化蛋白激酶(MAPK)和线粒体途径;用激光扫描共聚焦显微镜检测细胞内活性氧和线粒体膜的电位。结果 Twist1沉默显著增加了Panc-1细胞对吉西他滨的敏感性,JNK/线粒体的途径被激活,Twist1 siRNA诱导线粒体膜去极化同时显著上调线粒体分裂相关蛋白Fis1并降低融合相关蛋白Mfn1的表达。Twist1 siRNA提高了细胞内活性氧(ROS)的水平,与吉西他滨联合治疗进一步增加ROS。结论 siRNA介导的Twist1沉默在PANC-1细胞对吉西他滨化疗耐受中扮演了关键角色,Twist1沉默可能作为胰腺癌治疗的一种有效方法。
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