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国家自然科学基金(30871099)

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相关作者:陈小会钱文斌周郁鸿周秀杰更多>>
相关机构:海宁市人民医院杭州市第二人民医院浙江中医药大学更多>>
发文基金:国家自然科学基金杭州市卫生科技计划项目更多>>
相关领域:医药卫生更多>>

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Matrine and CYC116 Synergistically Inhibit Growth and Induce Apoptosis in Multiple Myeloma Cells被引量:3
2015年
Objective: To investigate whether CYC116 can potentiate matdne-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells. Methods: The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an M'I-F assay and apoptosis induction was evaluated by flow cytometry. Activation ot the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting. Results: Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor K B (NF-κB). Conclusions: CYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.
周郁鸿冯尽意尤良顺孟海涛钱文斌
关键词:APOPTOSISINHIBITORMATRINE
高三尖杉酯碱联合三氧化二砷诱导人多发性骨髓瘤RPMI 8226细胞株凋亡的实验研究被引量:5
2013年
目的通过体外实验阐述高三尖杉酯碱(HHT)单药及联合亚砷酸(ATO)用药对人多发性骨髓瘤细胞株RPMI8226作用及其机制。方法应用四甲基偶氮唑(MTT)比色法,检测HHT、ATO单药及两者联合用药对人多发性骨髓瘤细胞株RPMI8226增殖的影响,Hoechst染色法检测细胞凋亡形态学变化,流式细胞仪检测细胞早期凋亡比率。Western blot检测药物处理后凋亡关键蛋白(Caspase-3、9及PARP)、Bcl-2家族蛋白(Bcl-2、Mcl-1、Bcl-xl)及AKT蛋白的表达。结果 HHT、ATO单药可显著抑制RPMI8226细胞的增殖,其作用呈时间及浓度依赖(P<0.05),且两药联合具有协同作用(CI<1)。HHT、ATO单药可诱导RP-MI8226细胞凋亡且呈浓度依赖,出现细胞凋亡形态学改变及早期凋亡比率增高,两药联合可加强诱导凋亡作用。HHT可呈浓度依赖性激活Caspase-3、PARP表达;HHT(40ng/mL)与ATO(8.5μmol/L)联合用药可显著激活Caspase-3、9,下调抗凋亡蛋白Mcl-1及Bcl-xl的表达,呈时间依赖性降低AKT磷酸化水平。结论 HHT、ATO单药或联合用药可诱导RPMI8226细胞凋亡,其机制可能和激活Caspase通路、调节Bcl-2家族蛋白表达、抑制AKT磷酸化等有关。
周秀杰周郁鸿陈小会钱文斌
关键词:多发性骨髓瘤高三尖杉酯碱三氧化二砷细胞凋亡
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