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RPS27a沉默增强K562细胞对SAHA的药物敏感性
  • ISSN号:1009-2137
  • 期刊名称:《中国实验血液学杂志》
  • 时间:0
  • 分类:R733.72[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院,天津300020
  • 相关基金:国家自然科学基金(81270635,81300380);天津市应用基础研究计划重点项目(13JCZDJC29900)
中文摘要:

核糖体蛋白S27a(Ribosomal protein S27a,RPS27a),除了参与蛋白质合成外,还具有其他一些重要的核糖体外功能,如参与转录的调控和蛋白质翻译后的修饰.RPS27a在多种实体瘤组织、慢性髓系白血病(chronic myeloid leukemia,CML)加速期或急变期患者及急性白血病患者骨髓单个核细胞中高表达.本研究以CML急红变细胞系K562为细胞模型,研究RPS27a在K562细胞中的作用.应用shRNA干扰技术将K562细胞中RPS27a沉默,MTT法检测不同浓度组蛋白去乙酰化酶抑制剂N-辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)诱导RPS27a沉默后K562细胞的增殖变化,然后计算RPS27a沉默后K562细胞对SAHA的IC50,并采用Annexin V/PI双染法和细胞形态学检测SAHA诱导RPS27a沉默后K562细胞的凋亡.结果表明:RPS27a沉默明显降低K562细胞对SAHA的IC50 (P <0.01),并显著增加SAHA诱导K562细胞凋亡(P<0.01).结论:RP)S27a能抑制K562细胞的凋亡,RPS27a沉默增强K562细胞对SAHA的药物敏感性.

英文摘要:

Ribosomal protein $27a (RPS27a) can perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The RPS27a gene has been reported to be over- expressed in breast fibroadenomas, colorectal and renal cancers, advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. This study was purposed to explore the function of RPS27a in CML-erythroleukemia cell line K562 cells. RPS27a was silenced by short hairpin RNA (shRNA) in K562 cells. Furthermore, the proliferation changes of K562 cells was detected by MTT method after sliencing the RPS27a with suberoylanilide hydroxamic acid (SAHA), then the IC50 of K562-shl/sh2 and K562-scr cells to SAHA was measured. The results indicated that compared with K562-scr cells, the IC50 of K562-shl/sh2 to SAHA at 24 h and 48 h decreased (P 〈0.01 ); RPS27a slience significantly increased the percentage of apoptotic K562-shl/sh2 cells after incubation with 1μmol/L, 2 μmol/L and 5μmol/L SAHA for 24 h and 48 h as compared with that of K562-scr cells (P 〈 0.01 ). K562-shl, K562-sh2 and K562-scr cells after incubation with or without 2 μmol/L SAHA for 48 h presented apoptosis features: i. e. chromatin condensation, nucleic fragmentation and apoptotic body formation. It is concluded that RPS27a can inhibit the apoptosis of K562 cells and RPS27a slience can potentiate sensitivity of K562 cells to SAHA.

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期刊信息
  • 《中国实验血液学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中国病理生理学会
  • 主编:吴祖泽
  • 地址:北京海淀区永定路57号202-1
  • 邮编:100850
  • 邮箱:jexphema@263.net
  • 电话:010-66930873 68215932
  • 国际标准刊号:ISSN:1009-2137
  • 国内统一刊号:ISSN:11-4423/R
  • 邮发代号:2-389
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,美国生物医学检索系统,中国中国科技核心期刊,中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:12052