三氧化二砷阻滞人Burkitt淋巴瘤细胞增殖和细胞周期作用及其相关机制  

Blocking Effect of Arsenic trioxide on the Proliferation and Cell Cycle of Human Burkitt Lymphoma Cells and Its Related Mechanism

作　　者：陈亚娟[1] 李惠民[2] 陆维[1] 卿晨[1] 

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [2]昆明医科大学第一附属医院血液科,云南昆明650032

出　　处：《中国实验血液学杂志》2013年第6期1454-1459,共6页Journal of Experimental Hematology

基　　金：云南省科技厅应用基础研究面上项目(编号2011FZ100)

摘　　要：本研究探讨As2O3对人Burkitt淋巴瘤细胞增殖和细胞周期的影响及相关的分子机制,为As2O3临床应用于Burkitt淋巴瘤的治疗提供依据。以人Burkitt淋巴瘤Namalwa细胞株为模型,用不同浓度As2O3作用不同时间,以MTT法、流式细胞术、RQ-PCR和Western-blot分别检测As2O3对细胞增殖、增殖周期和凋亡发生及细胞周期重要调节基因CyclinE、CDK2和P21表达的影响。结果表明:As2O3显著抑制Namalwa细胞的生长增殖,并显示明显的浓度和时间依赖性;As2O3明显阻滞Namalwa细胞于G1期,并显示明显的量效关系;As2O3诱导Namalwa细胞凋亡,呈现明显的作用浓度和作用时间依赖性;As2O3明显下调Namalwa细胞CyclinE、CDK2基因的转录及蛋白表达,明显上调CDK抑制蛋白P21基因的转录及蛋白表达,且呈现出浓度依赖性。结论:As2O3明显抑制人Burkitt淋巴瘤细胞株Namalwa的生长增殖,此作用与As2O3阻滞细胞周期于G1期及诱导细胞凋亡有关,而As2O3对细胞周期的阻滞与其下调细胞周期的重要驱动基因CyclinE和CDK2的表达、上调CDK抑制因子P21基因的表达密切相关。This study was aimed to investigate the effect of arsenic trioxide （ As2O3） on proliferation and cell cycle of human Burkitt lymphoma cells and its related molecular mechanism, so as to provide experimental evidence for treatment of Burkitt lymphoma with As2O3. Human Burkitt lymphoma cell line Namalwa was used as the model, the effect of As2O3 on cell proliferation, cell cycle and apoptosis, as well as the expression of cell cycle modulation related genes, in- cluding mRNA and protein level, were detected by MTT method, flow cytometry, real-time quantitative PCR （RQ- PCR） and Western blot, respectively. The results showed that theAs2O3 inhibited significantly the growth and prolifera- tion of Namalwa cells in concentration-and time-dependent manner. TheAs2O3arrested obviously cell cycle of Namalwa cells in G1 phase, and showed significant concentration-effect relationship. TheAs2O3induced the apoptosis of Namalwa cells in concentration-and time-dependent manner, downregulated the expession of the important driving genes of cell cy- cle including Cyclin E and CDK2 in mRNA and protein level, upregulated the expession of the important inhibiting gene of cell cycle-P21 in mRNA and protein level in concentration-dependent manner. It is concluded thatAs2O3 inhibits significantly the growth and proliferation of Namaiwa cells, and the effect was closely relates with its inducing the apop- tosis and blocking the cell cycle of Namalwa. The action of blocking cell cycle is closely associated with its downregulat- ing the expession of driving genes of cell cycle--CyclinE and CDK2, upregulating the expession of the inhibiting gene of cell cycle-P21.

关 键 词：三氧化二砷 BURKITT淋巴瘤 细胞周期 细胞周期调节蛋白 

分 类 号：R733.1[医药卫生—肿瘤] R979.1[医药卫生—临床医学]