硼替佐米联合伊马替尼诱导K562细胞凋亡机制的研究

Study on mechanism of apoptosis by bortezomib and imatinib in K562 cells in vitro

目的研究硼替佐米（BOR）单独或联合伊马替尼（IM）对慢性粒细胞性白血病（CML）急变期细胞株K562凋亡的影响并探讨其可能的机制。方法不同浓度的BOR、IM处理K562细胞，于12、48、72h分别采用四甲基偶氮唑蓝比色法（MTT）检测细胞增生活性；流式细胞仪检测细胞凋亡；反转录聚合酶链反应（RT—PCR）法检测LivinmRNA的表达。结果MTT和流式细胞仪结果显示BOR单药可以抑制K562细胞增生，诱导其凋亡，并且能够增强IM对细胞的杀伤作用。RT-PCR结果显示BOR或IM可以下调LivinmRNA的表达，联合作用后，LivinmRNA的水平明显降低。结论BOR单药或联合IM可以诱导K562细胞的凋亡，其机制可能与下调LivinmRNA的表达有关，两药联合具有协同作用。

Objective To investigate the effect of bortezomib alone and in combination with imatinib on apoptosis of human chronic myeloid leukemia cells of the line K562 ,what is more, to explore the mechanism. Methods K562 was cultured and treated with hortezomib and （or） imatinib in different concentrations for 12, 48, 72 hours. Cell proliferation was analyzed by MTT assay, the apoptosis of K562 cells was observed by flow cytometry, and the expression of Livin mRNA was determined by reverse transcription polymerase chain reaction （RT-PCR）. Results MTr assay and flow cytometry showed that bortezomib could inhibit K562 cell proliferation and induce its apoptosis, and it can strengthen cells＇ lethal effect by imatinib. The expression of Livin mRNA was decreased by bortezomib or imatinib to some extent, and was downregulated significantly when. combined treatment was given. Conclusion Bortezomib alone and in combination with imatinib can induce K562 cells apoptosis, in which decrease of the expression of Livin mRNA is the possible mechanism.