中华医学杂志（英文版）2001，Vol.114Issue(1)：19-24,6.
氧化砷通过线粒体跨膜电位下降与激活Caspase-3诱导多发性骨髓瘤细胞凋亡
Arsenic trioxide induces multiple myeloma cell apoptosis viadisruption of mitochondrial transmembrane potentials and activation of caspase-3
摘要
Abstract
Objective To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. Methods Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. Results Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. Conclusion As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.关键词
氧化砷多发性骨髓瘤细胞凋亡线粒体跨膜电位Key words
arsenic trioxide/multiple myeloma/apoptosis/mitochondrial transmembrane potentials分类
医药卫生引用本文复制引用
贾培敏,陈国强,蔡循,王龙,沈玉雷,周励,余韵,陈赛娟,王振义,黄晓君,周宇红,杨洁,张学光..氧化砷通过线粒体跨膜电位下降与激活Caspase-3诱导多发性骨髓瘤细胞凋亡[J].中华医学杂志（英文版）,2001,114(1):19-24,6.基金项目
This work was partly supported by the National Natural Science Foundation of China (No. 39970312 and No. 39730270), National Outstanding Young Scientific Foundation of China (No. 39725011) （No. 39970312 and No. 39730270）
