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[1]尚 晋,王志红,陈志忠,等.热休克蛋白27通过降低内质网应激抑制硼替佐米诱导的骨髓瘤细胞凋亡[J].福建医科大学学报,2019,53(03):144-151.
 SHANG Jin,WANG Zhihong,CHEN Zhizhong,et al.Heat Shock Protein 27 Inhibits Bortezomib Induced Apoptosis of Myeloma Cells by Reducing Endoplasmic Reticulum Stress[J].Journal of Fujian Medical University,2019,53(03):144-151.
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热休克蛋白27通过降低内质网应激抑制硼替佐米诱导的骨髓瘤细胞凋亡(PDF)
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《福建医科大学学报》[ISSN:1672-4194/CN:35-1192/R]

卷:
第53卷
期数:
2019年03期
页码:
144-151
栏目:
论著
出版日期:
2019-06-30

文章信息/Info

Title:
Heat Shock Protein 27 Inhibits Bortezomib Induced Apoptosis of Myeloma Cells by Reducing Endoplasmic Reticulum Stress
文章编号:
672-4194(2019)03-0144-08
作者:
尚 晋1 王志红1 陈志忠2 魏天南 1 吴文冰2 陈为民1
福建医科大学 省立临床医学院,福建省立医院,福州 350001 1.血液科; 2.检验科
Author(s):
SHANG Jin1 WANG Zhihong1 CHEN Zhizhong2 WEI Tiannan1 WU Wenbing2 CHEN Weimin1
1. Fujian Medical University Shengli Clinical Medical College, Department of Hematology, Fujian Provincial Hospital, Fuzhou 350001, China; 2. Department of Laborato
关键词:
多发性骨髓瘤 热休克蛋白质类 内质网
Keywords:
multiple myeloma heat-shock proteins boron endoplasmic reticulum
分类号:
R341; R733.3; R916.3
DOI:
-
文献标志码:
A
摘要:
目的 探讨多发性骨髓瘤(MM)细胞热休克蛋白27(HSP27)表达对硼替佐米诱导凋亡的影响及机制。 方法 人MM细胞株U266细胞暴露于硼替佐米,实时荧光定量PCR检测HSP27 mRNA,蛋白质印迹法检测HSP27、磷酸化-HSP27(p-HSP27)、葡萄糖调节蛋白78(GRP78)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、活化的天冬氨酸特异性半胱氨酸蛋白酶3/9(cl-Caspase 3/9)表达。收集12例初治和10例复发MM患者骨髓瘤细胞,荧光原位杂交法检测染色体异常,比较HSP27 mRNA和蛋白表达差异。将U266细胞分为观察组和对照组,分别转染HSP27-siRNA和NC-siRNA,流式细胞术检测硼替佐米诱导的细胞凋亡率。慢病毒介导HSP27基因在U266细胞过表达,蛋白质印迹法检测硼替佐米诱导的GRP78和cl-Caspase 3表达。 结果 硼替佐米暴露显著上调U266细胞HSP27 mRNA和蛋白的表达(P<0.01),上调GRP78和p-PERK表达(P<0.05),活化Caspase-3和Caspase-9(P<0.05); 4-苯基丁酸预处理显著抑制硼替佐米诱导的Caspase-3和Caspase-9活化(P<0.01)。复发MM患者HSP27 mRNA和蛋白的表达显著高于初治MM患者(P<0.01)。沉默HSP27表达显著增加硼替佐米诱导的U266细胞凋亡(P<0.01)。慢病毒介导HSP27过表达显著抑制硼替佐米诱导的GRP78表达和Caspase-3活化(P<0.01)。 结论 HSP27负反馈抑制内质网应激,减少硼替佐米诱导的MM细胞凋亡。
Abstract:
Objective To investigate the effect of heat shock protein 27(HSP27)on bortezomib induced apoptosis of multiple myeloma cells and its mechanism. Methods The human multiple myeloma U266 cells were exposed to bortezomib, and HSP27 mRNA expression was measured by real-time fluorescent quantitative PCR. The expression of HSP27, p-HSP27, GRP78, p-PERK, cl-Caspase 3, and cl-Caspase 9 were determined by western blot analysis. Myeloma cells from 12 newly treated and 10 relapsed myeloma patients were collected, chromosomal abnormalities were detected by fluorescence in situ hybridization, and expression of HSP27 mRNA and protein were compared. HSP27-siRNA was transfected into U266 cells in observation group and NC-siRNA was transfected in control group, the apoptotic rate induced by bortezomib was detected by flow cytometry. Lentivirus-mediated overexpression of HSP27 gene in U266 cells, bortezomib-induced expression of GRP78, and cl-Caspase-3 were detected by western blotting. Results Bortezomib exposure significantly increased the expression of HSP27 mRNA and protein in U266 cells(P<0.01). Bortezomib exposure significantly increased the expression of GRP78, p-PERK, cl-Caspase-3, and cl-Caspase-9(P<0.05), while pretreatment with 4-phenylbutyric acid attenuated the effect of bortezomib exposure on activation of Caspase-3 and Caspase-9 of U266 cells(P<0.01). The expression of HSP27 mRNA and protein in relapsed multiple myeloma patients were significantly higher than that in newly treated multiple myeloma patients(P<0.01). Silencing the expression of HSP27 significantly increased the apoptosis of U266 cells induced by bortezomib(P<0.01). Lentivirus mediated HSP27 overexpression significantly inhibited bortezomib exposure induced GRP78 and cl-Caspase-3 expression in U266 cells(P<0.01). Conclusion HSP27 negative feedback inhibited endoplasmic reticulum stress and reduced bortezomib induced apoptosis of myeloma cells.

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备注/Memo

备注/Memo:
收稿日期: 2018-09-04基金项目: 福建省自然科学基金面上项目(2018J01259); 福建省卫计委医学创新基金(2018-CX-5)作者简介: 尚 晋,男,副主任医师,医学博士通讯作者: 陈为民. Email: chenwm1962@163.com
更新日期/Last Update: 2019-06-30