蛋白酶体抑制剂联合伊马替尼对K562细胞livin基因表达的影响

Effect of proteasome inhibitor combined with imatinib on expression of livin mRNA in K562 cells

目的研究蛋白酶体抑制剂硼替佐米(bortezomib,BOR)单独或联合伊马替尼(imatinib,IM)对慢性髓性白血病(chro-nic myelogenous leukemia,CML)急变期细胞株K562中livin mRNA表达的影响。方法不同浓度BOR(2.5,5,10nmol/L)和IM(0.25μmol/L)单药或分别联合处理K562细胞,分别于药物作用12,48,72h后采用逆转录聚合酶链反应(RT-PCR)方法检测livin mRNA的表达。结果BOR或IM单药组K562细胞中livin mRNA的表达下调,而且随着药物浓度的增加表达降低,且在药物作用48h时达最高。联合作用后,livin mRNA的下降水平显著增加。结论BOR单药或联合IM可以下调K562细胞中livin mRNA的表达,并可能通过此机制来诱导其凋亡,两药联合具有协同作用。

Objective To investigate the effect of bortezomib alone or combined with imatinib on the expressiom of livin mRNA in K562 cells. Methods K562 cells were cultured and treated with the different concentrations of bortezomib（2.5 nmol/L,5 nmol/L, 10 nmol/L）, imatinib（ 0.25 μmol/L） or their combination for 12,48 and 72 h. Then the expression of livin mRNA was detected by RT- PCR. Results The expression of livin mRNA decreased in a dose-dependent manner after treated with bortezomib or imatinib, and peaked at 48 h. And it was downregulated significantly after combined treatment. Conclusion Bortezomib and imatinib could induce apoptosis by inhibiting the expression of livin mRNA in K562 cells. Combination of bortezomib and imatinib have a synergistic effect.