吲哚美辛诱导慢性髓细胞白血病细胞凋亡的研究

Study of apoptosis induced by indomethacin in chronic myeloid leukemia

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。

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 ①IN induced apoptosis of K562 and fresh CML cells and inhibited the proliferation of K562 cells ②A synergic effect of inducing K562 cell apoptosis was observed when IN combined with Vp16 ③IN 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