中国中西医结合杂志2013，Vol.33Issue(6)：834-839,6.
高三尖杉酯碱联合三氧化二砷诱导人多发性骨髓瘤RPMI8226细胞株凋亡的实验研究
Homoharringtonine Combined Arsenic Trioxide Induced Apoptosis in Human Multiple Myeloma Cell Line RPMI 8226: an Experimental Research
摘要
Abstract
Objective To clarify the effects and mechanisms of homoharringtonine (HHT) monomer therapy or combination therapy with arsenic trioxide (ATO) on human multiple myeloma (MM) cell line RPMI 8226 in in vitro researches.Methods Effects of HHT,ATO,and HHT combined ATO on the growth of MM cell line RPMI 8226 were detected using MTT assay.The morphological changes of cell apoptosis were detected by Hoechst staining.The early apoptosis rate was detected using flow cytometry.Expressions of Caspase-3,Caspase-9,poly-ADP-ribose polymerase (PARP),Bcl-2,Mcl-1,Bcl-xl,and AKT protein were detected by Western blot.Results HHT and ATO inhibited the proliferation of RPMI 8226 cell line in a timeand dose-dependent manner (P ＜0.05).Synergistic effects was shown in the combination group (CI ＜1).HHT and ATO induced the apoptosis of RPMI 8226 in a dose-dependent manner with typical morphological changes of apoptosis and higher early stage apoptosis rate.The enhancement in apoptotic induction was seen when two agents were combined.HHT activated expressions of Caspase-3 and PARP in a dose dependent manner at 24 h.HHT at 40 ng/mL and ATO at 8.5 μmol/L could significantly activate expressions of Caspase-3 and Caspase-9,and down-regulate expressions of anti-apoptotic proteins Bcl-xl and Mcl-1.In addition,the combination therapy of HHT at 40 ng/mL and ATO at 8.5 μmol/L inhibited phosphorylation of AKT in a time-dependent manner.Conclusion HrT,ATO,and combination therapy of HHT and ATO induced the apoptosis of RPMI 8226 cell line possibly through activating Caspase pathways,regulating expressions of Bcl-2 families,and inhibiting phosphorylation of AKT.关键词
多发性骨髓瘤/高三尖杉酯碱/三氧化二砷/细胞凋亡Key words
multiple myeloma / homoharringtonine/ arsenic trioxide / apoptosis引用本文复制引用
周秀杰,周郁鸿,陈小会,钱文斌..高三尖杉酯碱联合三氧化二砷诱导人多发性骨髓瘤RPMI8226细胞株凋亡的实验研究[J].中国中西医结合杂志,2013,33(6):834-839,6.基金项目
国家自然科学基金资助项目(No.30871099) （No.30871099）
杭州市卫生科技计划资助项目(No.2011A016) （No.2011A016）
