CAJ | 학술논문

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
양화신통과선립체과막전위하강여격활Caspase-3유도다발성골수류세포조망
Arsenic trioxide induces multiple myeloma cell apoptosis viadisruption of mitochondrial transmembrane potentials and activation of caspase-3

万方数据

中华医学杂志(英文版) 中華醫學雜誌(英文版) 중화의학잡지(영문판)
CHINESE MEDICAL JOURNAL
2001年 1期 19-24 ,共6页

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

가배민%진국강%채순%왕룡%침옥뢰%주려%여운%진새연%왕진의%황효군%주우홍%양길%장학광

氧化砷多发性骨髓瘤细胞凋亡线粒体跨膜电位氧化砷多髮性骨髓瘤細胞凋亡線粒體跨膜電位
양화신다발성골수류세포조망선립체과막전위
arsenic trioxide%multiple myeloma%apoptosis%mitochondrial transmembrane potentials

目的探讨氧化砷(As2O3)是否诱导多发性骨髓瘤细胞凋亡与其可能机制。方法以两株多发性骨髓瘤细胞系RPMI8226和U266为体外模型。以细胞形态学观察、流式细胞仪检测亚G1期细胞含量以及DNA凝胶电泳判定细胞凋亡。通过检测胞内Rhodamine123染色强度来判定线粒体跨膜电位。通过Western印迹分析蛋白表达。结果 0.1-0.5?μmol/L As2O3抑制RPMI8226与U266细胞系生长，2.0?μmol/L As2O3诱导两株细胞凋亡，而1.0?μmol/L As2O3抑制细胞生长同时也诱导部分细胞凋亡。As2O3诱导的细胞凋亡伴随线粒体跨膜电位下降与细胞凋亡，而二巯基苏糖醇(二巯基还原剂)则部分抑制以上效应。虽然全反式维甲酸(ATRA)诱导RPMI8226细胞凋亡，但是它与As2O3无协同效应。结论不同深度As2O3可抑制多发性骨髓瘤细胞生长与诱导细胞凋亡。线粒体是As2O3诱导细胞凋亡的重要且共同的“靶子”。
목적탐토양화신(As2O3)시부유도다발성골수류세포조망여기가능궤제。 방법이량주다발성골수류세포계RPMI8226화U266위체외모형。이세포형태학관찰、류식세포의검측아G1기세포함량이급DNA응효전영판정세포조망。통과검측포내Rhodamine123염색강도래판정선립체과막전위。통과Western인적분석단백표체。 결과 0.1-0.5?μmol/L As2O3억제RPMI8226여U266세포계생장，2.0?μmol/L As2O3유도량주세포조망，이1.0?μmol/L As2O3억제세포생장동시야유도부분세포조망。As2O3유도적세포조망반수선립체과막전위하강여세포조망，이이구기소당순(이구기환원제)칙부분억제이상효응。수연전반식유갑산(ATRA)유도RPMI8226세포조망，단시타여As2O3무협동효응。 결론불동심도As2O3가억제다발성골수류세포생장여유도세포조망。선립체시As2O3유도세포조망적중요차공동적“파자”。
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.