FGFR抑制剂BGJ398对白血病细胞生物学行为及耐药的影响  

Effects of FGFR inhibitor BGJ398 on cell biological behavior and drug resistance of leukemia cells

作　　者：张艳君 李建厂[1] 贾秀红[1] 田春梅[1] ZHANG Yanjun;LI Jianchang;JIA Xiuhong;TIAN Chunmei(Department of Pediatrics,Binzhou Medical University Hospital,Binzhou 256603,Shandong Province,China)

机构地区：[1]滨州医学院附属医院儿科,山东滨州256603

出　　处：《中国癌症杂志》2021年第3期176-181,共6页China Oncology

基　　金：山东省医药卫生科技发展计划项目(2017WSB30031)。

摘　　要：背景与目的:成纤维细胞生长因子(fibroblast growth factor,FGF)家族成员能够调节细胞增殖、迁移和分化,在肿瘤性疾病的发生和转移等过程中发挥重要作用,FGF受体(FGF receptor,FGFR)抑制剂具有抗肿瘤活性。探讨FGFR抑制剂BGJ398对白血病耐药细胞株K562/ADM增殖、迁移、凋亡和耐药的影响。方法:将K562/ADM细胞分为空白对照组、阴性对照组和实验组,采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)法检测细胞的增殖抑制情况。采用transwell小室法检测BGJ398对白血病细胞迁移能力的影响。采用流式细胞术检测各组细胞的凋亡率。采用CCK-8法检测K562/ADM细胞对阿糖胞苷(cytarabine,Ara-c)、柔红霉素(daunorubicin,DNR)药物敏感性的变化。采用蛋白质印迹法(Western blot)测定FGFR抑制剂BGJ398对耐药细胞株MDR1耐药基因的影响。结果:FGFR抑制剂BGJ398能显著抑制K562/ADM细胞的增殖,并具有浓度依赖性,BGJ398的作用浓度分别为5、10、15 mol/L时抑制作用明显。实验组迁移细胞数为11.00±3.00,较阴性对照组(57.67±14.57)和空白对照组(43.00±4.00)明显减少(P<0.05)。实验组细胞凋亡率为(81.49±5.38)%,明显高于空白对照组(10.09±1.36)%和阴性对照组(7.64±1.32)%(P<0.001)。FGFR抑制剂能显著降低Ara-c、DNR对K562/ADM细胞的半数抑制浓度(half maximal inhibitory concentration,IC_(50));Western blot结果显示,BGJ398能显著降低耐药基因MDR1的蛋白表达水平,逆转白血病细胞耐药。结论:FGFR抑制剂BGJ398能有效地抑制白血病耐药细胞株K562/ADM的增殖和迁移,促进凋亡,逆转耐药,FGFR有望成为白血病治疗的新靶点。Background and purpose:Fibroblast growth factor(FGF)family members can regulate cell proliferation,migration and differentiation and play an important role in tumorigenesis and metastasis.FGF receptor(FGFR)inhibitors have anti-tumor activity.This study investigated the effects of FGFR inhibitor BGJ398 on proliferation,migration,apoptosis and drug resistance of leukemia cell line K562/ADM.Methods:K562/ADM cells were divided into blank control group,negative control group and experimental group.The inhibition of K56/ADM cell proliferation was detected by cell counting kit-8(CCK-8)assay,and the effect of BGJ398 on the migration ability of leukemia cells was detected by transwell assay.The apoptotic rate of each cell line was measured by flow cytometry,the sensitivity of K562/ADM cells to cytarabine(Ara-c)and daunorubicin(DNR)was detected by CCK-8 assay,and the effect of BGJ398 on MDR1 resistance gene was determined by Western blot.Results:The proliferation of K562/ADM cells was significantly inhibited by FGFR inhibitor BGJ398 in a concentration-dependent manner.BGJ398 inhibited K562/ADM cells at concentrations of 5,10 and 15μmol/L,respectively.Compared with the negative control group(57.67±14.57)and the blank control group(43.00±4.00),the number of transplanted cells in the experimental group was(11.00±3.00).The apoptotic rate in the experimental group was(81.49±5.38)%,compared with the control group(10.09±1.36)% and the negative control group(7.64±1.32)%(P<0.001).FGFR inhibitors significantly decreased the half maximal inhibitory concentration(IC50)of Ara-c and DNR to K562/ADM cells.Western blot showed that BGJ398 could significantly reduce the protein expression of MDR1 gene and reverse the drug resistance of leukemia cells.Conclusion:FGFR inhibitor BGJ398 can effectively inhibit the proliferation and migration of drug-resistant leukemia cell line K562/ADM,promote apoptosis and reverse drug resistance.FGFR may become a new target for the treatment of leukemia.

关 键 词：成纤维细胞生长因子受体抑制剂 K562/ADM细胞 白血病 

分 类 号：R733.7[医药卫生—肿瘤]