CAJ | 학술논문

目的了解三氧化二砷(As2O3) 诱导多发性骨髓瘤细胞（MM）凋亡的可能机制及其与维甲酸和干扰素的相互作用。方法联合应用As2O3和巯基还原剂（DTT）、谷胱甘肽耗竭剂（BSO）、全反式维甲酸（ATRA）或干扰素（IFN-α）处理MM细胞系RPMI8226和U266细胞；应用台盼蓝拒染法计数细胞活力，经细胞形态学和流式细胞仪等判定细胞凋亡的程度；通过测定细胞内荧光染料Rhodamine 123的色强度分析线粒体跨膜电位（ΔΨm）。结果 BSO可加强As2O3诱导的RPMI8226和U266细胞线粒体ΔΨm下降和凋亡，而DTT则有部分拮抗的作用。ATRA诱导RPMI8226细胞凋亡，但它和As2O3之间无协同效应。ATRA并不诱导U266细胞凋亡。此外，IFN-α既不抑制RPMI8226和U266细胞的生长和活力，也不改变As2O3对这些细胞的作用。结论 As2O3诱导多发性骨髓瘤细胞凋亡和巯基有关，但ATRA或干扰素和As2O3无协同效应。
목적료해삼양화이신(As2O3) 유도다발성골수류세포（MM）조망적가능궤제급기여유갑산화간우소적상호작용。방법연합응용As2O3화구기환원제（DTT）、곡광감태모갈제（BSO）、전반식유갑산（ATRA）혹간우소（IFN-α）처리MM세포계RPMI8226화U266세포；응용태반람거염법계수세포활력，경세포형태학화류식세포의등판정세포조망적정도；통과측정세포내형광염료Rhodamine 123적색강도분석선립체과막전위（ΔΨm）。결과 BSO가가강As2O3유도적RPMI8226화U266세포선립체ΔΨm하강화조망，이DTT칙유부분길항적작용。ATRA유도RPMI8226세포조망，단타화As2O3지간무협동효응。ATRA병불유도U266세포조망。차외，IFN-α기불억제RPMI8226화U266세포적생장화활력，야불개변As2O3대저사세포적작용。결론 As2O3유도다발성골수류세포조망화구기유관，단ATRA혹간우소화As2O3무협동효응。
Objective　To investigate the possible mechanisms of arsenic trioxide (As2O3)-induced apoptosis in multiple myeloma (MM) cell line, and the interactions between As2O3 and all-trans retinoic acid (ATRA) or interferon(IFN)-α.Methods　Multiple myeloma cell lines RPMI 8226 and U266 were treated with As2O3 in combination with dithiothreitol (DTT), buthionine sulfoximine (BSO), ATRA and IFN-α. Cell viability was counted by trypan-blue exclusion. Apoptosis was assessed by cell morphology and flow cytometry. Mitochondrial transmembrane potentials (ΔΨm) were measured by cellular rhodamine 123 staining intensity on flow cytometry.Results　Glutathione depleting agent BSO at 1.0 mmol/L enhanced, while disulfide bond-reducing agent DTT at 0.2 mmol/L partially antagonized As2O3-induced decline of ΔΨm and apoptosis in MM cells. ATRA also induced RPMI 8226 cell apoptosis, but it could not synergize with As2O3. On the other hand, As2O3-induced apoptosis did not occur in U266 cells. In addition, IFN-α itself did not inhibit the growth and viability of MM cells, nor did it influence the effects of As2O3 on MM cells.Conclusion　As2O3-induced apoptosis of RPMI 8226 multiple myeloma cells involves sulphyhydryl groups. ATRA and IFN-α do not synergize with As2O3 in the induction of apoptosis of MM cells.