硼替佐米对伊马替尼耐药细胞株K562的凋亡作用及机制

发布时间：2018-07-21 13:16

【摘要】：目的探讨硼替佐米对伊马替尼耐药细胞株K562(K562R)的诱导凋亡作用及机制。方法采用浓度梯增法建立耐伊马替尼K562细胞系。应用CCK-8法检测不同浓度硼替佐米分别作用K562和K562R细胞24 h、48 h后,对细胞的增殖抑制的效果。使用流式细胞术方法分别检测硼替佐米单独或联合伊马替尼作用于K562R细胞48 h后的细胞凋亡。应用Western blotting检测不同浓度硼替佐米作用K562R细胞48 h后,Mcl-1、Bcl-2、Bcr/Abl蛋白表达的异同。结果成功将对伊马替尼敏感的K562细胞诱导为K562R,耐药倍数为31.8;硼替佐米对K562及K562R细胞的增殖抑制呈浓度、时间依赖(P均0.05);随着硼替佐米浓度增加,对K562R细胞的诱导凋亡作用增强,且硼替佐米与伊马替尼联合具有协同作用(P0.05);硼替佐米可抑制K562R细胞Mcl-1,Bcr/Abl蛋白的表达,Bcl-2无变化。结论硼替佐米具有对K562R细胞的增殖抑制和诱导凋亡作用,其机制可能与下调K562R细胞Bcr/Abl和MCL-1的表达以及促进MCL-1发生切割有关。
[Abstract]:Objective to investigate the effect and mechanism of bortezomib on the induction of apoptosis of imatinib resistant cell line K562 (K562R). Methods the nimatinib K562 cell line was established by the concentration ladder method. The effect of different concentrations of bortezomib on the proliferation inhibition of K562 and K562R cells 24 h and 48 h, respectively, was detected by CCK-8 method. The apoptosis was detected by bortezomizomi alone or combined with imatinib after 48 h of K562R cells. Western blotting was used to detect the similarities and differences of Mcl-1, Bcl-2, and Bcr/Abl protein expression after 48 h of bortezomizomib at different concentrations. The results successfully induced the K562 cells of imatinib sensitivity to K562R and multidrug resistance. 31.8, bortezomib inhibited the proliferation of K562 and K562R cells in a concentration, time dependent (P, 0.05). With the increase of bortezomizomi, the induction of apoptosis in K562R cells was enhanced, and bortezomib combined with imatinib (P0.05). Bortezomizomi could inhibit the expression of Mcl-1, Bcr/Abl protein in K562R cells, and Bcl-2 was not changed. Conclusion bortezomib can inhibit the proliferation of K562R cells and induce apoptosis. The mechanism may be related to the downregulation of the expression of Bcr/Abl and MCL-1 in K562R cells and the promotion of MCL-1 cutting.
【作者单位】：广州医科大学附属第二医院血液科;广州医科大学附属第二医院血液实验室;
【基金】：广东省医学科学基金(A2014305)
【分类号】：R733.72

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