miR-449b对胶质瘤细胞替莫唑胺治疗敏感性的影响
首发时间:2017-05-16
摘要:目的:miR-449b在多种肿瘤细胞中都处于低表达状态,是潜在的肿瘤抑制因子。本课题主要探究miR-449b表达对胶质瘤细胞替莫唑胺(TMZ)治疗敏感性的的影响及内在的调控机制。方法:选用两株胶质瘤细胞,T98G和LN229,将miR-449b模拟剂转入这两种细胞中,采用MTT法、克隆集落法和免疫印迹法检测miR-449b表达对不同剂量TMZ处理后的胶质瘤细胞的存活、增殖能力和凋亡水平的影响;同时检测miR-449b表达对替莫唑胺治疗下胶质瘤细胞ATP水平的影响,以及将外源ATP脂质体转入后对细胞活力的影响。结果:MTT研究表明,增加miR-449b表达可降低替莫唑胺治疗下胶质瘤细胞的存活能力,表现为肿瘤细胞活力下调、克隆集落形成能力减弱及凋亡水平增加;ATP检测结果发现,miR-449b表达可降低替莫唑胺应激下肿瘤细胞ATP水平,并且外源性ATP补充可明显增强替莫唑胺治疗下肿瘤细胞的活力。结论:以上研究结果提示,miR-449b可通过加剧替莫唑胺治疗下胶质瘤细胞ATP水平消耗,进而促进胶质瘤细胞对替莫唑胺治疗的敏感性,有利于提高替莫唑胺对胶质瘤的治疗效果及其在临床上的应用
关键词: miR-449b 胶质瘤 替莫唑胺 敏感性 ATP
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The critical role of miR-449b in glioma cells sensitivity to TMZ
Abstract:OBJECTIVE: Mir-449b, a member of the miR-449 family, has been shown to be down-regulated in a variety of human malignancies, and to be a potential tumor suppressor. The aim of this study was to study the role of miR-449b in glioma cells sensitivity to TMZ, and the involved mechanism by which miR-449b contributes glioma cells sensitivity to TMZ therapy. METHODS: Cell biology, molecular biology, pharmacology experiment methods were used in this study. RESULTS: Ectopic expression of miR-449b with specific mimics significantly enhanced the cytotoxicity of TMZ therapy in glioma cells, as indicated by decreases in glioma cells viability and colony formation, and increase in the amount of cleaved PARP. ATP assay showed that miR-449b mimic greatly diminished ATP level, and exogenous ATP supplementation partially reduced the cytotoxicity effect of TMZ in glioma cells, CONCLUSION: These results suggest that promoting ATP depletion contribute to the miR-449b mediated TMZ-sensitivity.
Keywords: miR-449b glioma cells TMZ sensitivity ATP
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miR-449b对胶质瘤细胞替莫唑胺治疗敏感性的影响
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