摘要
目的 了解三氧化二砷 (As2 O3 )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As2 O3 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RPMI82 2 6和U2 6 6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 12 3的色强度分析线粒体跨膜电位 (ΔΨm)。结果 BSO可加强As2 O3 诱导的RPMI82 2 6和U2 6 6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RPMI82 2 6细胞凋亡 ,但它和As2 O3 之间无协同效应。ATRA并不诱导U2 6 6细胞凋亡。此外 ,IFN α既不抑制RPMI82 2 6和U2 6 6细胞的生长和活力 ,也不改变As2 O3 对这些细胞的作用。结论 As2 O3 诱导多发性骨髓瘤细胞凋亡和巯基有关 ,但ATRA或干扰素和As2 O3 无协同效应。
Objective To investigate the possible mechanisms of arsenic trioxide (As 2O 3) induced apoptosis in multiple myeloma (MM) cell line, and the interactions between As 2O 3 and all trans retinoic acid (ATRA) or interferon(IFN) α.Methods Multiple myeloma cell lines RPMI 8226 and U266 were treated with As 2O 3 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 As 2O 3 induced decline of ΔΨm and apoptosis in MM cells. ATRA also induced RPMI 8226 cell apoptosis, but it could not synergize with As 2O 3. On the other hand, As 2O 3 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 As 2O 3 on MM cells.Conclusion As 2O 3 induced apoptosis of RPMI 8226 multiple myeloma cells involves sulphyhydryl groups. ATRA and IFN α do not synergize with As 2O 3 in the induction of apoptosis of MM cells.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2001年第3期181-183,共3页
Chinese Journal of Oncology
基金
国家杰出青年科学基金资助项目(39725011)
国家自然科学基金资助项目(39670329)
重点项目(39730270)
上海市青年科技启明星计划资助项目(96OB14021)
卫生部青年基金部分资助(90Q-073)
