白血病
细胞凋亡
膜联蛋白
Jurkat细胞
化学
免疫印迹
流式细胞术
分子生物学
免疫学
癌症研究
生物
生物化学
T细胞
免疫系统
基因
作者
Tao Chen,Lie Li,Zhe Chen,Yu Hou
出处
期刊:PubMed
日期:2023-10-17
卷期号:31 (5): 1284-1289
标识
DOI:10.19746/j.cnki.issn.1009-2137.2023.05.005
摘要
To investigate the inhibitory effect of small molecule compound TIC10 on multiple leukemia cells and its intervention effect on acute myeloid leukemia(AML) induced by MLL-AF9.Leukemia cells (MOLM-13, MV4-11, THP-1, Kasumi-1, KG-1 and K562) were used to detect the inhibitory effect of TIC10 on proliferation of leukemia cells through CCK-8 and cell count. The effect of TIC10 on the cell-cycle of leukemia cells was detected by flow cytometry with BrdU and DAPI staining. Apoptosis was detected by Annexin V and PI staining. Western blot was used to detect the effect of TIC10 on the expression of caspase3, a key apoptosis-associated protein. The intervention effect of TIC10 on the progression of leukemia in vivo was detected by constructing a mouse MLL-AF9 leukemia model.TIC10 treatment significantly inhibited the proliferation of MOLM-13, MV4-11, THP-1, and Kasumi-1 cells(P<0.05). TIC10 treatment substantially reduced the incorporation of BrdU in MV4-11 and Kasumi-1 cells (P<0.01), suggesting that TIC10 inhibited S-phase entry of leukemia cells. Apoptosis assay showed that TIC10 obviously induced apoptosis of leukemia cells(P<0.01). Western blot results showed that TIC10 treatment induced an elevated cleaved-caspase3 protein level in leukemia cells(P<0.05). The results of animal experiments proved that TIC10 effectively interfered with the progression of AML in vivo .TIC10 can effectively inhibite the proliferation of leukemia cells and induce apoptosis, and have a certain intervention effect on AML induced by MLL-AF9, indicating that TIC10 as a potential candidate drug for the treatment of leukemia.小分子化合物TIC10对白血病细胞的抑制作用.研究小分子化合物TIC10对多种白血病细胞的抑制作用及其对MLL-AF9诱发的急性髓系白血病的干预效果.采用MOLM-13、MV4-11、THP-1、Kasumi-1、KG-1和K562细胞,通过CCK-8和细胞计数检测TIC10对白血病细胞增殖的影响。BrdU和DAPI染色的流式细胞术检测TIC10对白血病细胞周期的影响。Annexin V和PI染色检测TIC10对白血病细胞凋亡的影响。Western blot检测TIC10对白血病细胞凋亡关键蛋白Caspase3表达的影响。构建小鼠MLL-AF9白血病模型以检测TIC10对急性髓系白血病在体进展的干预效果.TIC10处理均显著抑制MOLM-13、MV4-11、THP-1和Kasumi-1细胞的增殖(P<0.05)。TIC10处理使MV4-11及Kasumi-1细胞中的BrdU掺入显著减少(P<0.01),表明TIC10阻碍白血病细胞进入 S期。凋亡实验结果显示,TIC10能显著诱导白血病细胞凋亡(P<0.01)。免疫印迹结果表明,TIC10促进多种白血病细胞中Cleaved-Caspase3蛋白水平的增加(P<0.05)。动物实验结果证实TIC10能有效干预小鼠体内白血病的进展.TIC10能有效抑制白血病细胞的增殖并诱导细胞凋亡,对MLL-AF9诱发的急性髓系白血病有一定干预效果,TIC10有望作为白血病治疗的潜在候选药物.
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