Effects of enhancer of Zeste homolog 2 inhibitor GSK126 on the cell proliferation and apoptosis of acute leukemia and lymphoma cells in vitro
10.3760/cma.j.issn.1009ˉ9921.2019.05.005
- VernacularTitle:Zeste基因增强子同源物2抑制剂GSK126体外对急性白血病和淋巴瘤细胞增殖及凋亡的影响
- Author:
Yuqiao GAO
1
;
Qi ZHANG
;
Qi HAN
;
Jie ZI
;
Jinlong MA
;
Zheng GE
Author Information
1. 东南大学附属中大医院血液科 东南大学血液病研究所
- Keywords:
Hematologic neoplasms;
Cell proliferation;
Apoptosis;
Enhancer of Zeste homolog 2;
GSK126
- From:
Journal of Leukemia & Lymphoma
2019;28(5):276-281
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of a novel enhancer of Zeste homolog 2 (EZH2) inhibitor GSK126 in vitro on the cell proliferation and apoptosis in acute leukemia and lymphoma cells. Methods CCKˉ8 assay was used to measure the effects of GSK126 with different concentrations and time on the cell proliferation in human Tˉcell acute lymphoblastic leukemia (TˉALL) CEM cell line, acute monocytic leukemia U937 cell line and Burkitt lymphoma Raji cell line. Annexin V/PI double staining method was used to determine the effects of GSK126 on the cell apoptosis. The effect of GSK126 on the mRNA levels of EZH2, bclˉ2 and bclˉxL were measured by using quantitative polymerase chain reaction (qPCR). Results After the function for 24 h, 48 h and 72 h, compared to the negative control group (0 μmol/L), 5, 10, 15, 20, 25 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in CEM cells; 5, 10, 15, 20 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in U937 cells; 5, 10, 15, 20, 25, 30 μmol/L GSK126 treatment showed a significant timeˉdependent suppression in Raji cells (all P< 0.05). The 48 h 50% inhibitory concentration ( IC 50) of GSK126 on CEM, U937, Raji cells was (13.46 ±0.83), (11.65 ±1.02), (15.00 ±0.19) μmol/L, respectively. GSK126 treatment with the doses of 8, 12 and 16 μmol/L promoted the apoptosis of CEM and U937 cells compared with the negative control group (0 μmol/L), and there were statistical differences in the apoptosis rate (F= 167.995, P< 0.01; F= 158.400, P< 0.01). In Raji cells, only 16 μmol/L GSK126 treatment had a higher cell apoptosis rate compared with the control group (t= 47.998, P< 0.05). Furthermore, 8, 12 and 16 μmol/L GSK126 treatment suppressed the expressions of EZH2 mRNA in CEM, U937 and Raji cells compared with the control group (F=82.035, P<0.01; F= 252.712, P< 0.01; F= 690.536, P< 0.01), and the expressions of bclˉ2 and bclˉxL mRNA (bclˉ2: F= 1 900.525, P< 0.01; F= 431.324, P< 0.01; F=216.184, P<0.01; bclˉxL: F=256.751, P<0.01; F=147.019, P<0.01; F=209.325, P<0.01). Conclusion EZH2 plays an important role in the occurrence and development of acute leukemia and lymphoma. GSK126 as a high selective inhibitor of EZH2 might be a potential new drug in treatment of hematological malignancies.