吲哚美辛对CML细胞增殖抑制效应与STAT信号转导途径抑制相关

Proliferation inhibiting Effect of Indomethacin on Chronic Myeliod Leukemia Cells is Related to the Supression of STAT Signal Transduction Pathway

本研究的目的是观察吲哚美辛作用下慢性粒细胞白血病 (CML)细胞增殖抑制过程中JAK2、STAT1和STAT5蛋白质表达水平的变化及细胞内分布 ,揭示吲哚美辛抑制CML细胞增殖的分子机制。采用MTT及台盼蓝拒染法检测吲哚美辛对CML细胞的增殖抑制作用 ,用Westernblot分析CML细胞JAK2、STAT1和STAT5蛋白质表达 ,用间接免疫荧光技术观察STAT1和STAT5在吲哚美辛干预的CML细胞中的定位及变化。结果表明 :4 0 0 μmol/L浓度的吲哚美辛能明显抑制CML细胞增殖及STAT1、STAT5蛋白质表达 ,但对JAK2蛋白无影响 ;STAT1和STAT5主要分布于细胞胞浆中。结论 :吲哚美辛可抑制CML细胞增殖 ,其机制可能与药物下调STAT1、STAT5蛋白质表达或与阻断细胞生长信号传导有关。

This study was aimed to observe whether expressions of JAK2, STAT1, STAT5 proteins in indomethacin treated CML cells involved in the proliferation inhibition of CML cells, and elucidate the pharmacological mechanism of indomethacin anti leukemia. MTT assay and trypan blue dye exclusion test were used to detect the inhibitory effect of indomethacin on CML cells proliferation. JAK2, STAT1, STAT5 proteins were analyzed by Western blot; the subcellular distribution of STAT1, STAT5 were detected with indirect immunofluorescence technique. The results showed that indomethacin at ≥400 μmol/L significantly inhibited the proliferation of CML cells and down regulated the expression of STAT1, STAT5 protein, no JAK2 change was observed. STAT1 and STAT5 were located in cytoplasm. It is concluded that indomethacin inhibits the proliferation of CML cells and the mechanism may be related to down regulated expression of STAT, or blockage of cells growth signals.