中国药理学通报2017，Vol.33Issue(2)：185-190,6.DOI:10.3969/j.issn.1001-1978.2017.02.009
阿司匹林诱导EB病毒转化的人B淋巴细胞凋亡
Mechanisms of aspirin-induced apoptosis in EBV-transformed human B lymphocytes
摘要
Abstract
Aim To investigate the effects of aspirin on Epstein-Barr virus (EBV)-transformed human B-lym-phocytes.Methods EBV-transformed human B-lym-phocytes were treated with certain concentrations of as-pirin.Cellular proliferation was analyzed by MTT as-say.Further evaluation of apoptosis of aspirin-treated cells was performed through light-field microscope, transmission electronic microscope(TEM),propidium iodide(PI)staining and flow cytometric analysis and DNA electrophoresis. Finally, immunoblot analysis was used to determine the expression levels of apopto-sis-associated proteins, proteins involved in mTOR pathway and PU.1 -Bim axis.Results Aspirin treat-ment inhibited proliferation of EBV-transformed human B-lymphocytes.We observed that aspirin treatment in-duced apoptosis in EBV-transformed human B-lympho-cytes,resulting in the decreased number and size of cells.Ultramicroscopic structural analysis via TEM in-dicated that aspirin treatment deformed the cellular nu-cleus,and led to peripheral chromatin and cytoplasmic vacuole.PI staining and flow cytometric analysis indi-cated that aspirin increased the permeability of cell membrane and decreased the viability of treated cells. Agarose electrophoresis revealed DNA smear in aspirin-treated cells.Mechanistically,mTOR signaling was in-hibited in aspirin-treated cells,as evidenced by the de-creased phosphorylation of S6K1 and S6 via immunob-lot analysis.Aspirin treatment led to the decrease of hematopoietic transcription factor PU.1 .Consequently, pro-apoptotic Bim, apoptosis-associated proteins caspase-3 and PARP were activated in aspirin-treated cells.Conclusion Aspirin may show anti-lymphoma effects via its inhibition of proliferation and induction of apoptosis of EBV-transformed human B-lymphocytes, in which mTOR signal pathway and PU.1 -Bim axis may be involved.关键词
阿司匹林/EB 病毒转化的人 B 淋巴细胞/凋亡/mTOR/PU.1 -Bim 轴/抗肿瘤Key words
aspirin/EBV-transformed human B-lym-phocytes/apoptosis/mTOR/PU.1 -Bim axis/anti-tumor分类
医药卫生引用本文复制引用
陶玉芬,刘波,李超,李昕潼,刘建生,杨昭庆,刘红旗..阿司匹林诱导EB病毒转化的人B淋巴细胞凋亡[J].中国药理学通报,2017,33(2):185-190,6.基金项目
国家自然科学基金资助项目（No 81571549）；云南省应用基础研究计划项目（No 2013FZ143）；云南省重点新产品开发专项项目（No 2016BC004）；医学生物学研究所重点项目 （）
