塞利尼索联合伊马替尼对K562/G01细胞的增殖及凋亡的影响  

Effect of selinexor combined with imatinib on proliferation and apoptosis of K562/G01 cells

作　　者：郝晓静 马梁明[2] HAO Xiaojing;MAO Liangming(Third Hospital of Shanxi Medical University/Shanxi Bethune Hospital/Shanxi Academy of Medical Sciences/Tongji Shanxi Hospital,Taiyuan 030032;Department of Hematology,Third Hospital of Shanxi Medical University/Shanxi Bethune Hospital/Shanxi Academy of Medical Sciences,Taiyuan 030032,China)

机构地区：[1]山西医科大学第三医院/山西白求恩医院/山西医学科学院/同济山西医院,山西太原030032 [2]山西医科大学第三医院/山西白求恩医院/山西医学科学院/同济山西医院血液内科,山西太原030032

出　　处：《西安交通大学学报（医学版）》2024年第3期405-410,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：山西省回国留学人员科研资助项目(2017-126)。

摘　　要：目的观察塞利尼索(selinexor,SEL)联合伊马替尼(imatinib,IM)对人慢性髓原白血病细胞耐伊马替尼(K562/G01,KG)细胞株的增殖及凋亡的影响,探索其可能的作用机制。方法分别用IM、SEL单独或联合处理人慢性髓系白血病(K562)细胞株及KG细胞株,采用MTT法检测细胞活力,流式细胞术检测细胞凋亡率,RT-PCR法检测细胞的BCR-ABL mRNA表达,Western blotting法检测细胞的XPO1蛋白表达。结果IM、SEL均可抑制K562细胞和KG细胞的增殖,作用48 h的半数抑制浓度IC50分别为IM(0.16μmol/L vs.6.48μmol/L),SEL(132.0 nmol/L vs.275.9 nmol/L);SEL联合IM作用于KG细胞,与单用相比,可明显抑制KG细胞的增殖(P<0.05),促进KG细胞的凋亡(P<0.05),降低KG细胞BCR-ABL mRNA(P<0.05),抑制KG细胞XPO1的表达(P<0.05)。结论SEL联合IM可协同抑制KG细胞的增殖并诱导其凋亡,进而抑制BCR-ABL mRNA和XPO1蛋白的表达,发挥抗白血病作用。Objective To observe the effect of Selinexor(SEL)combined with Imatinib(IM)on the proliferation and apoptosis of Imatinib-resistant chronic myeloid leukemia K562/G01(KG)cells and explore the possible mechanisms.Methods K562 cells and KG cells were treated with SEL or IM respectively or in combination.Cells viability was examined by MTT assay.Apoptosis was assessed by flow cytometry.BCR-ABL mRNA was detected by RT-PCR.XPO1 was detected by Western blotting.Results IM and SEL both inhibited the proliferation of K562 cells and KG cells;half maximal inhibitory concentration(IC50)for 48 h was 0.16μmol/L vs.6.48μmol/L for IM and 132.0 nmol/L vs.275.9 nmol/L for SEL.Compared with SEL or IM alone,SEL combined with IM significantly inhibited the proliferation of KG cells(P<0.05),induced KG cells apoptosis(P<0.05),downregulated the levels of BCR-ABL mRNA(P<0.05),and inhibited the expressions of XPO1 in KG cells(P<0.05).Conclusion SEL combined with IM can synergistically inhibit the proliferation and induce apoptosis of KG cells,and then inhibit the expressions of BCR-ABL mRNA and XPO1 to exert an anti-leukemia effect.

关 键 词：塞利尼索 慢性髓系白血病 K562/G01 伊马替尼耐药 细胞凋亡 

分 类 号：R733.72[医药卫生—肿瘤]