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LSP1抑制万珂诱导的多发性骨髓瘤细胞凋亡(英文)
引用本文:方颖慧,任子甲,马佳佳,郭雨刚,赵莹,徐璐,方芳,王永庆,肖卫华.LSP1抑制万珂诱导的多发性骨髓瘤细胞凋亡(英文)[J].中国科学技术大学学报,2010,40(4).
作者姓名:方颖慧  任子甲  马佳佳  郭雨刚  赵莹  徐璐  方芳  王永庆  肖卫华
作者单位:1. 合肥微尺度物质科学国家实验室,中国科学技术大学生命科学学院,安徽合肥,230027
2. 安徽省医科大学血液病科,安徽合肥,230022
基金项目:Supported by National Natural Science Foundation of China(30771973,30721002); National Key Basic Research (973) Program(2007CB914503)
摘    要:淋巴细胞特异性蛋白-1(LSP1)在部分多发性骨髓瘤中表达升高,但其在肿瘤中的作用仍知之甚少.研究了LSP1在多发性骨髓瘤中抗新型抗肿瘤药物万珂(Bortezomib)诱导细胞凋亡的作用及机制.筛选LSP1高表达和低表达的多发性骨髓瘤细胞IM9和KAS6作为实验模型.应用RNA干扰基因沉默IM9细胞中的LSP1,或在KAS6细胞中转染LSP1表达质粒,用Bortezomib等化疗药物处理细胞后,PI/Annexin V染色并用流式细胞仪检测和分析细胞凋亡率.同时RT-PCR方法检测和分析被LSP1所影响的重要细胞凋亡相关基因的变化.结果发现,LSP1在多发性骨髓瘤细胞IM9和KAS6中差异性表达高和低,与Bortezomib诱导的细胞凋亡效率密切相关.利用RNA干扰敲低IM9细胞中LSP1,可显著增强IM9对Bortezomib的敏感性,同时在KAS6中转染LSP1表达质粒,可降低Bortezomib诱导的细胞凋亡.对部分重要凋亡基因的RT-PCR检测发现,LSP1可诱导BCL-xl基因表达,同时抑制p53表达.因此,发现LSP1可通过调节凋亡基因的表达促进肿瘤的抗药性.

关 键 词:药物耐受性  凋亡

Leukocyte-specific protein 1 inhibits Bortezomib induced apoptosis in multiple myeloma cells
FANG Yinghui,REN Zijia,MA JIajia,GUO Yugang,ZHAO Ying,XU Lu,FANG Fang,WANG Yongqing,XIAO Weihua.Leukocyte-specific protein 1 inhibits Bortezomib induced apoptosis in multiple myeloma cells[J].Journal of University of Science and Technology of China,2010,40(4).
Authors:FANG Yinghui  REN Zijia  MA JIajia  GUO Yugang  ZHAO Ying  XU Lu  FANG Fang  WANG Yongqing  XIAO Weihua
Institution:FANG Yinghui1,REN Zijia1,MA JIajia1,GUO Yugang1,ZHAO Ying1,XU Lu1,FANG Fang1,WANG Yongqing2,XIAO Weihua1(1.Hefei National Laboratory for Physical Sciences at Microscale,, School of Life Sciences,University of Science , Technology of China,Hefei 230027,China,2.Department of Hemotology,the First Affiliated Hospital,Anhui Medical University,Hefei 230022,China)
Abstract:To investigate the roles of anti-apoptosis by leukocyte-specific protein 1(LSP1) in Multiple Myeloma cells(MM),RT-PCR and immunoblotting were used to assess the gene expression in MM cell lines,IM9 and KAS6.Plasmids containing either sh-RNA targeting LSP1 or full-length cDNA coding for human LSP1 were constructed and transfected into IM9 and KAS6 cells,respectively.Cell apoptosis rate induced by Bortezomib was measured by PI/Annexin V staining and FACS assay.The results shows that LSP1 is highly expressed i...
Keywords:LSP1  Bortezomib  LSP1  Bortezomib  drug resistant  apoptosis
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