Aurora激酶抑制剂VX-680对慢性髓系白血病细胞增殖及凋亡的影响

Effect of Aurora Inhibitor VX-680 on Proliferation and Apoptosis of CML Cells

本研究探讨Aurora激酶抑制剂VX-680在体外对白血病细胞系K562、KCL22和慢性髓系白血病(CML)患者骨髓CD34+细胞的增殖和凋亡的影响。利用CCK-8法观察VX-680对K562和KCL22细胞的增殖作用,细胞计数方法测定VX-680对CML的CD34+细胞增殖影响,Annexin V-PI凋亡检测试剂盒、流式细胞术分析VX-680对K562、KCL22细胞凋亡效应,集落形成试验检测VX-680对CML及正常供者(donor)的骨髓CD34+细胞集落形成能力影响。结果表明,Aurora激酶抑制剂VX-680(20-100 nmol/L)在处理细胞第3天时能明显抑制K562和KCL22细胞增殖(P<0.01),并能抑制CML患者骨髓CD34+细胞增殖,而且随着剂量增加,抑制作用增强;VX-680(20nmol/L)作用K562和KCL22细胞3天时可诱导细胞凋亡(P<0.01);集落形成试验表明,CML患者骨髓CD34+细胞在VX-680的体外处理下集落形成能力较正常骨髓CD34+细胞明显下降(P<0.01)。结论:Aurora激酶抑制剂VX-680在体外对慢性髓系白血病细胞有抑制增殖和促进凋亡的作用。

This study was aimed to explore the effect of VX-680 an aurora inhibitoron proliferation and apoptosis of K562KCL22 cell lines and CD34^＋ cells from chronic myeloid leukemia（CML）patients in vitroThe proliferation of K562 and KCL22 cell was detected by CCK-8 method.Apoptosis of cells was detected by Annexin V-PI labeling and flow cytometry.The colony forming ability of bone marrow CD34^＋ cells derived from CML patients and donors was determined by the colony forming test.The results showed that the treatment of K562KCL22 and CML CD34^＋ cells with VX-680 of 20- 100 nmol /L for 3 days could obviously inhibit the cell proliferation in a concentration-dependent manner（ P〈0.01）.VX-680 treatment significantly induced apoptosis of K562 and KCL22 cells.Compared to bone marrow CD34^＋ cells derived from the healthy donorsthe colony forming ability of CML CD34^＋ cells derived from bone marrow of CML patients was remarkably reduced（P〈0.01）.It is concluded that VX-680 an aurora inhibitorcan inhibit the proliferation and induce apoptosis of CML cells in vitro.