涂传清 张广森 卢汉波 410011长沙，湖南医科大学附属第二医院分子血液病研究室、血液科 中华血液学杂志 1999 0 20 7


    关键词：吲哚美辛；白血病，髓样，慢性；细胞凋亡；细胞增殖；基因，bcl-2 期刊 zhxyxzz 0 论著 fur -->


    

摘要 目的观察和确定吲哚美辛(IN)对慢性髓细胞白血病(CML)细胞凋亡的诱导作用，并部分揭示其分子机制，以期筛选一种新的抗白血病药物。方法以CML细胞株K562及来自6例初治Ph+CML患者骨髓原代培养细胞为研究材料，在不同时间点，用不同浓度的IN进行干预，利用细胞形态学、流式细胞仪、DNA电泳、逆转录-聚合酶链反应(RT-PCR)等技术，确定IN对CML细胞凋亡和增殖的影响。结果①IN能诱导K562细胞和原代培养的CML细胞凋亡，并有抑制白血病细胞增殖的作用；②IN对足叶乙甙诱导K562细胞凋亡具有协同作用；③IN能下调K562细胞中bcl-2mRNA水平表达，对baxmRNA水平无明显影响。结论IN能诱导CML细胞凋亡和抑制白血病细胞增殖，IN对足叶乙甙的抗白血病效应具有增敏作用。bcl-2基因表达下调可能为IN诱导CML细胞凋亡的重要机制之一。

Study of apoptosis inducedby indomethacin in chronic myeloid leukemia

TU Chuanqing ZHANG Guangsen LU Hanbo

    Laboratory of Molecular Hematology, Division of Hematology, The Second AffiliatedHospital, Hunan Medical University, Changsha 410011

Abstract Objective To explore the effect of indomethacin(IN) on theapoptosis of chronic myeloid leukemia(CML) cells, and its molecular mechanisms, for thepurpose of screening a new antileukemic agent. Methods CML cell line K562 and fresh bonemarrow cells from 6 untreated Ph+ CML patients were used for in vitro culture study. Theeffects of IN on cells were determined by cell morphology, flow cytometry, DNAelectrophoresis, and RT-PCR. Results ① IN induced apoptosis of K562 and fresh CML cellsand inhibited the proliferation of K562 cells. ② A synergic effect of inducing K562 cellapoptosis was observed when IN combined with Vp16. ③ IN down-regulated the level ofbcl-2 mRNA without changing the level of bax mRNA in K562 cells. Conclusion IN can induceapoptosis and inhibit proliferation in CML cells, and increase the sensitivity of CMLcells to Vp16. Down-regulation of bcl-2 mRNA may be one of the mechanisms of CML cellapoptosis induced by IN.

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