Effect of bortezomib on reverse multidrug resistance and XIAP expression in imatinib-resistant primary cells of chronic myeloid leukemia in blastic crisis

Abstract

This study was aimed to explore the effects of proteasome inhibitor bortezomib on the drug sensitivity of imatinib-resistant primary cells in blastic phase of chronic myeloid leukemia (CML) and the expression of XIAP. MTT method was used to detect the inhibitory effect on cell growth, flow cytometry was used to assay the apoptosis and P170 expression, and RT-PCR was used to monitor the expression of XIAP mRNA. The results showed that the effect of imatinib or bortezomib alone showed an inhibitory effect on MNC in time-and dose-dependent manner; 5 and 10 nmoL/L bortezomib combined with imatinib could significantly enhance the sensitivity of mononuclear cells to imatinib. The increase of apoptosis rate, and the decrease of P170 expression could be observed by flow cytometry during treatment with bortezomib. The over-expression of XIAP could be down regulated by bortezomib. It is concluded that the bortezomib could inhibit primary cells of leukemia and enhance sensitivity of CML primary cells to imatinib.The bortezomib may increase the cell apoptosis by inhibition of XIAP expression, so as to provide the experiment evidence to spread bortezomib for the clinical treatment of chronic myeloid leukemia.