糖原合成酶激酶3抑制剂对伊马替尼诱导的慢性粒细胞白血病K562细胞增殖和凋亡的影响  

Effects of glycogen synthase kinase 3 inhibitors on the proliferation and apoptosis of chronic myelogenous leukemia K562 cells induced by imatinib

作　　者：梁家仪 陈运贤 Liang Jiayi;Chen Yunxian(Department of Pediatric Hematology,Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences,Guangzhou 510120,China;Guangzhou Chen Yunxian Life Science Corporation,Guangzhou 501660,China)

机构地区：[1]广东省人民医院广东省医学科学院儿童血液科,广州510120 [2]广州陈运贤生命科技有限公司,501660

出　　处：《白血病．淋巴瘤》2020年第10期581-585,共5页Journal of Leukemia & Lymphoma

摘　　要：目的探讨糖原合成酶激酶3(GSK3)抑制剂对伊马替尼诱导的慢性粒细胞白血病K562细胞增殖和凋亡的影响。方法1μmol/L伊马替尼分别联合不同浓度的GSK3抑制剂氯化锂(1.0、2.0、4.0 mmol/L)、SB216763(0.5、1.0、5.0μmol/L)及TWS119(0.5、1.0、5.0μmol/L)作用于K562细胞,分别以1μmol/L伊马替尼为相应对照组。用CCK-8法检测细胞增殖活性,流式细胞术检测细胞凋亡,蛋白质印迹法检测细胞内Wnt-β-catenin通路相关蛋白水平的变化。结果1μmol/L伊马替尼分别联合浓度梯度的SB216763、氯化锂、TWS1193组与对照组间K562细胞存活率差异均有统计学意义(均P<0.01)。1μmol/L伊马替尼+1.0μmol/L SB216763组、1μmol/L伊马替尼+5.0μmol/L SB216763组细胞存活率分别为(73.6±3.0)%、(77.0±3.6)%,均较对照组细胞存活率[(68.0±2.8)%]高(均P<0.05);1μmol/L伊马替尼+0.5μmol/L SB216763组细胞存活率为(70.0±2.2)%,与对照组比较差异无统计学意义(P>0.05)。1μmol/L伊马替尼+2.0 mmol/L氯化锂组、1μmol/L伊马替尼+4.0 mmol/L氯化锂组细胞存活率分别为(75.5±3.6)%、(83.4±3.9)%,均较对照组细胞存活率[(69.5±2.1)%]高(均P<0.05);1μmol/L伊马替尼+1.0 mmol/L氯化锂组[(72.3±6.0)%]与对照组间细胞存活率差异无统计学意义(P>0.05)。1μmol/L伊马替尼分别联合0.5、1.0、5.0μmol/L TWS119组细胞存活率分别为(70.0±1.1)%、(72.1±0.8)%、(73.8±0.7)%,均较对照组[(67.9±7.5)%]高(均P<0.01)。1μmol/L伊马替尼+5.0μmol/L SB216763、1μmol/L伊马替尼+4.0 mmol/L氯化锂、1μmol/L伊马替尼+5.0μmol/L TWS119三组细胞凋亡率分别为(18.16±3.59)%、(20.11±2.98)%、(16.27±2.36)%,均较对照组[(28.26±2.20)%]低,差异均有统计学意义(均P<0.05)。与单独伊马替尼作用K562细胞相比,伊马替尼分别联合3个GSK3抑制剂作用的K562细胞中t-GSK3β、t-GSK3α蛋白表达水平无差异,p-GSK3β、p-GSK3α、β-catenin蛋白表达水平升高。结论GSK3抑制剂可减弱伊马替尼对�Objective To explore the effects of glycogen synthase kinase 3 (GSK3) inhibitors on the proliferation and apoptosis of chronic myelogenous leukemia (CML) K562 cells induced by imatinib.Methods K562 cells were treated with 1 μmol/L imatinib combined with GSK3 inhibitor lithium chloride with different concentrations of 1.0, 2.0, 4.0 mmol/L, SB216763 with different concentrations of 0.5, 1.0, 5.0 μmol/L andTWS119 with different concentrations of 0.5, 1.0, 5.0 μmol/L, and then 1μmol/L imatinib was used as the control group. The proliferation activity of K562 cells was determined by using CCK8 assay. Flow cytometry was used to detect the cell apoptosis. The level changes of Wnt-β-catenin pathway related-protein were analyzed by using Western blot.Results There were statistically significant differences of K562 cell survival rate between 1 μmol/L imatinib combined with different concentrations of SB216763, lithium chloride, TWS1193 groups and the control groups (all P < 0.01). The cell survival rate of 1 μmol/L imatinib + 1.0 μmol/L SB216763 group, 1 μmol/L imatinib + 5.0 μmol/L SB216763 group was (73.6±3.0)%, (77.0±3.6)%, which was higher than that of the control group [(68.0±2.8)%], and the difference was statistically significant (both P < 0.05). The cell survival rate of 1 μmol/L imatinib + 0.5 μmol/L SB216763 group was (70.0±2.2)%, and there was no statistical difference between 1 μmol/L imatinib + 0.5 μmol/L SB216763 group and the control group (P > 0.05). The cell survival rate of 1 μmol/L imatinib + 2.0 mmol/L lithium chloride group and 1μmol/L imatinib + 4.0 mmol/L lithium chloride group was (75.5±3.6)%, (83.4±3.9)%, which was higher than that of the control group [(69.5±2.1)%], and the difference was statistically significant (both P < 0.05);there was no statistical difference in the cell survival rate of 1 μmol/L imatinib + 1.0 mmol/L lithium chloride group [(72.3±6.0)%] and the control group (P > 0.05). The cell survival rate of 1 μmol/L imatinib combined with 0.5, 1.0, 5.0 μmol/L

关 键 词：白血病 髓系 慢性 BCR-ABL 糖原合成酶激酶3 蛋白激酶抑制剂 Β连环素 细胞凋亡 细胞增殖 伊马替尼 

分 类 号：R733.72[医药卫生—肿瘤]