阿司匹林诱导EB病毒转化的人B淋巴细胞凋亡

发布时间：2018-08-20 13:53

【摘要】：目的探讨阿司匹林诱导EB病毒转化的人B淋巴细胞凋亡及其机制。方法 EB病毒转化的人B淋巴细胞经一定浓度的阿司匹林处理后,首先通过MTT法分析细胞的增殖情况;然后用光学显微镜和电子显微镜、PI染色和流式细胞术分析以及琼脂糖凝胶电泳等方法对细胞凋亡进行评价;最后,通过免疫印记法检测凋亡相关蛋白、mTOR信号通路和PU.1-Bim信号通路蛋白表达情况。结果阿司匹林能抑制EB病毒转化的人B淋巴细胞增殖。形态学和超微结构观察发现,阿司匹林处理的细胞固缩变小、数目减少、细胞核畸形、染色质边缘化和细胞质空泡化。阿司匹林处理导致细胞膜通透性增加、细胞存活率明显下降和细胞DNA的弥散现象。免疫印迹分析显示,阿司匹林处理抑制了细胞的mTOR信号和转录因子PU.1的表达水平,激活了细胞凋亡相关蛋白caspase-3、PARP和Bim。结论阿司匹林可能通过抑制EB病毒转化的人B淋巴细胞增殖和诱导细胞凋亡表现一定的抗淋巴瘤效应,mTOR信号途径和PU.1-Bim轴可能参与了阿司匹林抗肿瘤作用机制。
[Abstract]:Objective to investigate the apoptosis of human B lymphocytes transformed by Epstein-Barr virus (EBV) induced by aspirin and its mechanism. Methods Epstein-Barr virus transformed human B lymphocytes were treated with aspirin at a certain concentration. The proliferation of B lymphocytes was analyzed by MTT assay. Then the apoptosis was evaluated by optical microscope, electron microscope, Pi staining, flow cytometry and agarose gel electrophoresis. The protein expression of apoptosis-related protein (mTOR) and PU.1-Bim signal pathway (PU.1-Bim) were detected by immunoblotting. Results Aspirin could inhibit the proliferation of human B lymphocytes transformed by EB virus. Morphologic and ultrastructural observation showed that the cells treated with aspirin had smaller pyknosis, decreased number, nuclear malformation, chromatin marginalization and cytoplasmic vacuolation. Aspirin treatment resulted in increased cell membrane permeability, decreased cell survival and dispersion of cell DNA. Western blot analysis showed that aspirin treatment inhibited the expression of mTOR signal and transcription factor PU.1, and activated the apoptosis-related proteins caspase-3 PARP and Bim. Conclusion Aspirin may be involved in the anti-tumor mechanism of aspirin by inhibiting the proliferation of human B lymphocytes transformed by EB virus and inducing apoptosis.
【作者单位】：中国医学科学院北京协和医学院医学生物学研究所;
【基金】：国家自然科学基金资助项目(No81571549) 云南省应用基础研究计划项目(No2013FZ143) 云南省重点新产品开发专项项目(No2016BC004) 医学生物学研究所重点项目(No2014IMB03ZD)
【分类号】：R96

【相似文献】