吲哚美辛诱导慢性髓细胞白血病细胞凋亡的研究

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K5 6 2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K5 6 2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K5 6 2细胞凋亡具有协同作用 ;③IN能下调K5 6 2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 induced by indomethacin in chronic myeloid leukemia

OBJECTIVE: To explore the effect of indomethacin(IN) on the apoptosis of chronic myeloid leukemia(CML) cells, and its molecular mechanisms, for the purpose of screening a new antileukemic agent. METHODS: CML cell line K562 and fresh bone marrow cells from 6 untreated Ph+ CML patients were used for in vitro culture study. The effects of IN on cells were determined by cell morphology, flow cytometry, DNA electrophoresis, and RT-PCR. RESULTS: 1. IN induced apoptosis of K562 and fresh CML cells and inhibited the proliferation of K562 cells. 2. A synergic effect of inducing K562 cell apoptosis was observed when IN combined with Vp16. 3. IN down-regulated the level of bcl-2 mRNA without changing the level of bax mRNA in K562 cells. CONCLUSION: IN can induce apoptosis and inhibit proliferation in CML cells, and increase the sensitivity of CML cells to Vp16. Down-regulation of bcl-2 mRNA may be one of the mechanisms of CML cell apoptosis induced by IN.