[S1PR2拮抗剂JTE-013对慢性粒细胞白血病细胞增殖的抑制作用]

[Inhibitory Effect of S1PR2 Antagonist JTE-013 on Proliferation of Chronic Myeloid Leukemia Cells].

作者信息

Pang Meng, Li Fang, Wang Jing, Jing Hong-Mei

机构信息

Department of Hematology, The Third Hospital of Peking University, Beijing 100191, China.

Department of Hematology, The Third Hospital of Peking University, Beijing 100191, China,E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Aug;28(4):1081-1085. doi: 10.19746/j.cnki.issn.1009-2137.2020.04.002.

DOI:10.19746/j.cnki.issn.1009-2137.2020.04.002

PMID:32798381

Abstract

OBJECTIVE

To investigate the effect of sphingosine-1-phosphate receptor 2 (S1PR2) specific antagonist JTE-013 on the proliferation of human chronic myeloid leukemia (CML) cell line K562.

METHODS

K562 cells were treated with JTE-013 (0, 0.5, 1, 5, 10, 20 μmol/L) for 24 and 48 hours respectively, CCK8 assay was used to detect the cell viability. K562 cells were treated with JTE-013 (0, 5, 10, 20 μmol/L) for 24 hours, propidium iodide (PI) DNA staining was used to analyze the cell cycle, Western blot was used to determine the levels of P21 and Cyclin D1 protein expression.

RESULTS

JTE-013 inhibited the proliferation of CML cell line K562 in a dose dependent manner (r=-0.971). The proliferation rate of CML cells showed that the activity of CML cells decreased gradually with the increase of JTE-013 concentration (r=-0.971). The detection demonstrated that JTE-013 suppressed tumor cell proliferation through cell cycle arrest in G/G phase. Further detection of the protein expressions of G phase regulators showed that level of P21 increased, and expression of Cyclin D1 decreased.

CONCLUSION

JTE-013, a S1PR2 antagonist, can inhibit the proliferation of human CML K562 cells, which may be achieved by arresting the cells in G/G phase.

摘要

目的

探讨1-磷酸鞘氨醇受体2（S1PR2）特异性拮抗剂JTE-013对人慢性髓系白血病（CML）细胞系K562增殖的影响。

方法

K562细胞分别用JTE-013（0、0.5、1、5、10、20μmol/L）处理24小时和48小时，采用CCK8法检测细胞活力。K562细胞用JTE-013（0、5、10、20μmol/L）处理24小时，采用碘化丙啶（PI）DNA染色分析细胞周期，采用蛋白质免疫印迹法检测P21和细胞周期蛋白D1蛋白表达水平。

结果

JTE-013以剂量依赖性方式抑制CML细胞系K562的增殖（r=-0.971）。CML细胞的增殖率表明，随着JTE-013浓度的增加，CML细胞活性逐渐降低（r=-0.971）。检测表明，JTE-013通过使细胞周期停滞在G/G期来抑制肿瘤细胞增殖。进一步检测G期调节因子的蛋白表达表明，P21水平升高，细胞周期蛋白D1表达降低。