内科理论与实践2009，Vol.4Issue(4)：295-299,5.
硼替佐米联合二硫化二砷诱导慢性粒细胞白血病细胞凋亡机制研究
Effect of bortezomib combined with arsenic disulfide on induction of apoptosis in chronic myeloid leukemic cells
摘要
Abstract
Objective To study the effect of bortezomib combined with arsenic disulfide (As2S2) on growth inhibition and apoptosis of two kinds of homologous chronic myeloid leukemic (CML) cell line K562 and K562R, sensitive or resistant to imatinib, respectively. Methods Tetrazolium-based eolorimetric assay (MTT), Giemsa stain cell morphology observation and Annexin V flow cytometry were used to assess the effects of bortezomib and As2S2, in single use or in combination, on inhibition of proliferation and induction of apoptosis in CML cell line. The effects on Bcr-Abl and apoptosis-related proteins was evaluated by Western blot analysis and expression of Bcr-Abl Mrna was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Results Bortezomib and As-As2S2 exerted synergistic effects on growth inhibition in both the K562 and K562R cell lines. The growth inhibition rate was over 70% and the rate of dead and apoptosis cells reached 54% in K562 cell line after treated with 6 nmol/L bortezomib plus 3 μmol/L As2S2 for 48 h. The difference was statistically significant (P<0.05) when compared with these drugs in single use. In K562R cell line, the growth inhibition rate was about 55% and the rate of dead and apoptosis cells was 38% after treated with 12 nmol/L bortezomib plus 6 μmol/L As2S2 for 48 h, and the difference was also statistically significant when compared with these drugs in single use (P<0.05). Combined use of bortezomib and As-As2S2 induced apoptosis by mitochondfial dependent apoptosis pathway, decreased Bcr-Abl protein expression and level of protein phosphorylation in both the K652 and K652R cell lines. Conclusions Combined use of bortezomib and As2S2 has significant synergistic growth inhibiting effect and apoptosis inducing effect both on imatinib-sensitive K562 and imatinib-resistant K562R cells. This combination regimen may be a potential therapeutic remedy for overcoming the imatinib resistance.关键词
慢性粒细胞白血病/凋亡/Bcr-Abl/硼替佐米/二硫化二砷Key words
Chronic myeloid leukemia/Apoptosis/Bcr-Abl/Bortezomib/Arsenic disulfide分类
医药卫生引用本文复制引用
陈丽,王爱华,陈雪瑜,阎骅,李军民..硼替佐米联合二硫化二砷诱导慢性粒细胞白血病细胞凋亡机制研究[J].内科理论与实践,2009,4(4):295-299,5.基金项目
国家自然科学基金资助(项目编号:30570777) （项目编号:30570777）
国家自然科学基金资助(项目编号:30700334) （项目编号:30700334）
上海市科委重点攻关项目(项目编号:08431900700) （项目编号:08431900700）
