吉林大学学报（医学版）Issue(3)：534-538,5.DOI:10.13481/j.1671-587x.20140314
二甲双胍对巨核细胞白血病细胞株Dami细胞增殖的抑制作用及其机制
Inhibitory effect of metformin on proliferation of megakaryocytic leukemia cell line Dami and its mechanism
摘要
Abstract
Objective To study the effect of metformin on the growth of megakaryocytic leukemia cell line Dami and to explore the molecular mechanisms of the inhibitory effect of metformin on the proliferation of Dami. Methods The Dami cells were cultured and divided into control and 1,2,4,8,16 and 32 mmol·L-1 metformin groups.Then MTT test was performed to detect the inhitory rate of proliferation of Dami cells after treated with different concentrations of metformin. Flow cytometry was used to examine the distribution of cell cycle, and Western blotting was carried out to analyze the expressions of Cdc2 and CylinB1 and the phosphorylation of Cdc2. Results The MTT results showed that compared with control group,the inhibitory rates of proliferation of the Dami cells in 32 mmol·L-1 metformin groups at 0,24,48,72 and 96 h (35.1%±2.3%,49.7%±5.1%, 78.85±0.9%,79.1%± 3.0%%,and 85.2%± 3.2%)were significantly increased(P<0.01),Furthermore, after metformin treatment for 72 h,the inhibitory rates of proliferation of the Dami cells in 1,2,4,8,16 and 32 mmol·L-1 metformin groups were (33.8 ± 0.3)%,(51.9 ± 0.2)%,(59.4 ± 1.6)%,(65.5 ± 2.0)%, (75.5±0.9)%,and (79.1±3.0)%,respectively. Metformin inhibited the growth of Dami cells in a time-and dose-dependent manner. The flow cytometry results results revealed that compared with control group, the percentages of Dami cells in G2/M phase in 1,2 and 4 mmol·L-1 metformin groups were increased from (26.0± 0.5)% to (38.5 ± 1.5 )%, (48.4 ± 1.1 )%, and (58.2 ± 2.7 )%;there was significant difference in the percentages of Dami cells in G2/M phase between control group and 4 mmol·L-1 metformin group (P<0.01). Western blotting analysis showed that compared with control group, the expressions of Cdc2 and CyclinB were evidently reduced, the phosophorylation of Cdc2 at Tyr1 5 was up-regulated, and the phosphorylation at Thr1 6 1 was down-regulated.Conclusion Metformin can inhibit the growth of Dami cells and induce G2/M arrest,and its mechanism may be related to inhibiting the activation of Cdc2/CyclinB1 complex.关键词
二甲双胍/白血病,原始巨核细胞,急性/细胞周期/Dami细胞Key words
metformin/leukemia,megakaryoblastic,acute/cell cycle/Dami cells分类
医药卫生引用本文复制引用
李长岭,蔺迪,邢思宁,赵松,陈惠鹏,周凡,马东初..二甲双胍对巨核细胞白血病细胞株Dami细胞增殖的抑制作用及其机制[J].吉林大学学报（医学版）,2014,(3):534-538,5.基金项目
科技部“十二五”重大新药创制国家科技重大项目资助课题 （）
