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靶向GRP78增强小鼠抗TfR单克隆抗体抑制神经胶质瘤细胞增殖

Targeting GRP78 enhances inhibition of murine monoclonal antibody against TfR on proliferation of glioma cells

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【作者】 文雪沈关心

【Author】 WEN Xue;SHEN Guan-xin;Department of Basic Medicine, School of Nursing, Hubei Polytechnic Institute;Department of Immunology,Basic Medical School, Tongji Medical College, Huazhong University of Science and Technology;

【通讯作者】 文雪;

【机构】 湖北职业技术学校护理学院基础教研室华中科技大学同济医学院基础医学院免疫学系

【摘要】 目的研究抗转铁蛋白受体(TfR)抗体作用于胶质瘤细胞是否会诱导内质网(ER)应激,以及靶向应激分子葡萄糖调节蛋白78(GRP78)能否促进抗TfR抗体的抗瘤效应。方法 Western blot检测抗TfR抗体作用胶质瘤细胞后GRP78和CHOP的表达。构建针对GRP78的小干扰RNA,小干扰RNA转染胶质瘤细胞后与抗TfR抗体共孵育,流式细胞计量术(FCM)检测肿瘤细胞的增殖和凋亡。结果抗TfR抗体能够诱导ER应激反应,提高胶质瘤细胞GRP78和CHOP的表达水平。与对照组相比,转染针对GRP78的小干扰RNA的胶质瘤细胞与抗TfR抗体作用后,增殖显著减少,凋亡显著增加(P<0.05)。结论抗TfR抗体的抗肿瘤作用触发了内质网应激反应,沉默应激分子GRP78的表达,可增强抗TfR抗体的抗瘤效应。

【Abstract】 Objective To investigate whether the anti-TfR antibody may lead to increased ER stress, and if anti-TfR antibody may inhibite proliferation of glioma cell by targeting at GRP78. Methods Western blot analysis was done to detecte the expression of GRP78 and CHOP after cells were treated with anti-TfR mAb. FCM was performed to detecte the proliferation and apoptosis of cells after transfection with siRNA and treated with anti-TfR mAb. Results Compared with the control groups, the anti-TfR antibody elevated expression GRP78 and CHOP. After glioma cells transfected with small interfering RNA(siRNA) against GRP78 showed lower proliferation and higher apoptosis rate when incubated with anti-TfR antibody. Conclusions Anti-TfR antibody has triggered the ER stress response, and that this effect is achieved via the siRNA against GRP78 for glioma cell proliferation and survival.

【关键词】 转铁蛋白受体胶质瘤葡萄糖调节蛋白78
【Key words】 TfRgliomaGRP78
【基金】 湖北省卫生与计划生育委员会青年人才项目(WJ2017Q040)
  • 【文献出处】 基础医学与临床 ,Basic & Clinical Medicine , 编辑部邮箱 ,2019年10期
  • 【分类号】R730.51
  • 【被引频次】1
  • 【下载频次】97
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