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蛋白酶体抑制剂PS-341诱导骨髓瘤细胞凋亡的蛋白质组学研究(英文)

Proteomics of apoptosis of multiple myeloma cells induced by proteasome inhibitor PS-341
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摘要 目的:比较蛋白酶体抑制剂PS-341处理多发性骨髓瘤细胞U266前后蛋白质组的差异,探究PS-341潜在的药物靶点,为多发性骨髓瘤的临床治疗提供理论依据。方法:用蛋白酶体抑制剂PS-341处理骨髓瘤细胞U266,应用双向凝胶电泳技术分离PS-341处理前后的U266细胞的蛋白质,Im-ageMaster 2D Platinum图像分析软件识别药物处理前后U266细胞的差异表达蛋白质点,基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)鉴定差异表达的蛋白质。Western印迹法检测差异蛋白质BAG-2在药物处理前后U266细胞中的表达水平。结果:建立了PS-341处理前后U266细胞蛋白质的双向凝胶电泳图谱,找到55个差异表达的蛋白质点,鉴定了31个差异表达的蛋白质,有27个蛋白质在PS-341处理后下调。Western印迹分析证实BAG-2在药物处理前后U266细胞中的表达水平存在差异。结论:处理后下调的一些蛋白可能是蛋白酶体抑制剂PS-341潜在的药物靶标。 Objective To compare the proteome difference between multiple myeloma cell line U266 cells treated and untreated with PS-341,to investigate the potential drug targets,and to provide theoretical evidence for clinical therapy of multiple myeloma.Methods Two-dimensional gel electrophoresis(2-DE) was performed to separate proteins from treated and untreated U266 cells with proteasome inhibitor PS-341.ImageMaster 2D Platinum software was used to analyze 2-DE image,and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) was used to identify the differentially expressed proteins.The expression levels of differential protein BAG-2 in the 2 groups of U266 cells lines were detected by Western blot.Results The 2-DE reference pattern of treated and untreated U266 cells with PS-341 was established.A total of 31 differential proteins were identified by MALDI-TOF-MS,27 of which were down-regulated after PS-341 treatment.The differential expression level of BAG-2 in the 2 groups of U266 cells was confirmed by Western blot.Conclusion Some down-regulated proteins may be the potential drug targets of proteasome inhibitor PS-341.
出处 《中南大学学报(医学版)》 CAS CSCD 北大核心 2010年第8期784-791,共8页 Journal of Central South University :Medical Science
关键词 PS-341 多发性骨髓瘤 双向凝胶电泳 质谱 药物靶标 PS-341 multiple myeloma 2-dimensional gel electrophoresis mass spectrome-try drug target
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  • 1邱录贵,麦玉洁.多发性骨髓瘤[M].上海:上海科学技术出版社,2006:789-812.
  • 2Anderson K C.Multiple myeloma:Advances in disease biology:therapeutic implication[J].Semin Hematol,2001,38 (2 Suppl 3):6210.
  • 3Hideshima T,Chauhan D,Schlossman R,et al.The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma:therapeutic applications[J].Oncogene,2001,20(33):4519-4527.
  • 4Hideshima T,Chauhan D,Richardson P,et al.NF-kappa B as a therapeutic target in multiple myeloma[J].J Biol Chem,2002,277(19):16639-16647.
  • 5Mitsiades N,Mitsiades C S,Poulaki V,et al.Molecular sequelae of proteasome inhibition in human multiple myeloma cells[J].Proc Natl Acad Sci U S A,2002,99(22):14374-14379.
  • 6Hideshima T,Richardson P,Chauhan D,et al.The proteasome inhibitor PS-341 inhibits growth,induces apoptosis,and overcomes drug resistance in human multiple myeloma cells[J].Cancer Res,2001,61(7):3071-3076.
  • 7王晖,刘心.多发性骨髓瘤的发病机制及药物治疗进展[J].国际病理科学与临床杂志,2006,26(5):403-406. 被引量:6
  • 8Qin J Z,Ziffra J,Stennett L.Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells[J].Cancer Res,2005,65(14):6282-6293.
  • 9Arndt V,Daniel C,Nastainczyk W,et al. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP[J].Mol Biol Cell,2005,16(12):5891-5900.
  • 10Dai Q,Qian S B,Li H H,et al.Regulation of the cytoplasmic quality control protein degradation pathway by BAG2[J].J Biol Chem,2005,280(46):38673-38681.

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