BMT-1抑制急性淋巴细胞白血病细胞增殖活力及其机制研究

发布时间：2018-05-08 15:37

本文选题：BMT-1 + 急性淋巴白血病　；参考：《成都医学院》2017年硕士论文

【摘要】：目的BMT-1属于苯并咪唑类双环化合物。大量研究表明,BMT-1可通过诱导肿瘤细胞凋亡来发挥其抗肿瘤功效,但目前尚未见BMT-1在急性B淋巴母细胞白血病中的研究。因此,本研究拟探讨BMT-1对B淋巴母细胞在增殖活力、凋亡以及线粒体膜电位等方面的影响,旨在为临床抗急性淋巴细胞白血病药物开发应用提供科学理论依据。方法以Daudi、Nalm6细胞为研究对象,使用不同浓度的BMT-1处理细胞后,检测各项指标的变化。(1)采用CCK8试剂盒检测BMT-1对细胞增殖活力的影响;(2)使用倒置荧光显微镜观察BMT-1对细胞密度的影响;(3)运用凋亡检测试剂盒(含PI、Annexin V)对BMT-1作用后的细胞进行凋亡检测;(4)流式细胞术检测细胞线粒体膜电位的变化情况;(5)Western Blot检测PARP及其相关蛋白表达水平。结果(1)BMT-1能显著抑制Daudi、Nalm6细胞的增殖活力;(2)BMT-1可显著降低Daudi细胞的细胞密度,细胞密度的下降可作为BMT-1具细胞毒性的佐证;(3)BMT-1可明确诱导Daudi细胞凋亡;(4)BMT-1可引起线粒体膜电位变化,且呈剂量依赖效应,提示BMT-1可通过线粒体途径诱导Daudi细胞凋亡;(5)BMT-1诱导Daudi细胞产生PARP剪切体,该剪切体的出现进一步证明BMT-1可诱导Daudi细胞凋亡。结论BMT-1能有效的抑制B淋巴母细胞的增殖活力;我们对其相关机制进行研究后发现,BMT-1可通过诱导细胞凋亡来实现其细胞增殖抑制活性;同时,我们通过显微镜观察发现,BMT-1能降低Daudi细胞的细胞密度;BMT-1也可引起线粒体膜电位及细胞PARP相关蛋白水平的变化。
[Abstract]:Objective BMT-1 belongs to benzimidazole bicyclic compounds. A large number of studies have shown that BMT-1 can induce apoptosis of tumor cells to play its anti-tumor effect, but no study of BMT-1 in acute B-lymphoblastic leukemia has been reported. Therefore, the purpose of this study was to investigate the effects of BMT-1 on the proliferation, apoptosis and mitochondrial membrane potential of B lymphoblastic cells in order to provide a scientific basis for the development and application of anti-acute lymphoblastic leukemia drugs. Methods Nalm6 cells were treated with different concentrations of BMT-1. CCK8 kit was used to detect the effect of BMT-1 on cell proliferation activity. The effect of BMT-1 on cell density was observed by inverted fluorescence microscope. The apoptosis detection kit (including Pi Annexin V) was used to detect the effect of BMT-1 on cell density. The changes of mitochondrial membrane potential were detected by flow cytometry. Western Blot was used to detect the expression of PARP and its related proteins. Results BMT-1 could significantly inhibit the proliferative activity of Daudi Nalm6 cells. The decrease of cell density in Daudi cells could be used as evidence of the cytotoxicity of BMT-1. The decrease of BMT-1 could definitely induce apoptosis of Daudi cells and induce mitochondrial membrane potential changes. In a dose-dependent manner, BMT-1 could induce apoptosis of Daudi cells through mitochondrial pathway. Daudi cells were induced to produce PARP shearing bodies by BMT-1, which further demonstrated that BMT-1 could induce apoptosis of Daudi cells. Conclusion BMT-1 can effectively inhibit the proliferation of B lymphoblastocytes. It was found that BMT-1 could decrease the cell density of Daudi cells and induce the change of mitochondrial membrane potential and PARP related protein level.
【学位授予单位】：成都医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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