姜黄素在CML原代细胞STAT5信号途径中的作用

Effect of Curcumin on STAT5 Signaling Pathway in Primary CML Cells

为了研究姜黄素对慢性粒细胞白血病 (CML)原代细胞信号转导和转录激活因子 5 (signaltransducersandactivatorsoftranscription5 ,STAT5 )信号途径的影响 ,并探讨姜黄素治疗CML的临床意义 ,将实验分为三组 :正常对照组 ,CML细胞组和姜黄素组。运用噻唑蓝 (MTT)比色法检测细胞的增殖活性 ,运用半定量逆转录聚合酶链式反应 (RT PCR)检测细胞STAT5mRNA的变化 ,运用电泳迁移率改变分析法 (electrophoreticmobilityshiftassay ,EMSA)检测细胞STAT5活化水平。结果表明 :姜黄素组细胞增殖活性 (OD值 0 .6 4 0± 0 .0 73)低于CML细胞组(0 85 6± 0 .0 83) ,差异有显著性意义 (P <0 .0 1)。CML细胞组STAT5mRNA(光密度积分比值 1.782± 0 .15 6 )较正常对照组 (光密度积分比值 0 .2 89± 0 .0 2 5 )明显增高 (P <0 .0 1) ,姜黄素组细胞STAT5mRNA(光密度积分比值1.398± 0 .12 6 )低于CML细胞组 ,差异有显著性意义 (P <0 .0 1)。CML细胞组STAT5活化水平 (灰度面积值5 32 3.375± 5 15 .6 4 0 )明显高于正常对照组 (灰度面积值 2 94 3.0 0 0± 2 73.377) ,差异有显著性意义 (P <0 .0 1)。姜黄素组细胞STAT5活化水平 (灰度面积值 4 331.75 0± 398.0 35 )低于CML细胞组 ,差异有显著性意义 (P <0 0 1)。结论 :CML原?

To study the effect of curcumin on signaling pathway of signal transduc ers and activators of transcription (STAT5) in primary newly-diagnosed chronic mye locytic leukemia (CML) cells, and to explore the clinical significance of curc umin in the treatment of primary CML cells, the cells were randomly divided into 3 groups: normal control group, CML cells group, and curcumin group; the cellular proliferation was assayed by MTT test; the expression of cellular STAT?5 mRNA in CML cells was detected by RT-PCR; the activation of STAT5 in CML cell was de tected by electrophoretic mobility shift assay (EMSA). The results showed that the cellular proliferation of cu rcumin group (OD value 0.640±0.073) was decreased, as compared with that of the CML cells group (OD value 0.856±0.083, P<0 01). The expression levels o f STAT5 mRNA in CML cells group (integral ratio of OD 1.782±0.156) wer e significantly greater than that in the normal control group (integral ratio of OD 0.289±0.025, P<0.01). The expression of STAT5 mRNA in curcumin group (integral ratio of OD 1.398±0.126) was significantly decreased as com pared with that in the CML cells group (P<0.01). The activation of STAT5 was significantly increased in CML cells group (gray value 5323.375±51 5.640) as compared with that in the normal control group (gray value 2943.000 ±273.377, P<0.01). The activation of STAT5 of curcumin group (gray value 4331.750±398.035) was significantly decreased as compar ed with that of CML cells group (P<0.01). It is concluded that the cellular prolif eration and th e expression of STAT5 mRNA are increased in the primary CML cells. The activatio n of STAT5 in primary CML cells is markedly enhanced. STAT5 signaling pathway ma y be involved in the proliferation of primary CML cells. Curcumin can inhibit t h e cellular proliferation and the expression of STAT5 mRNA, and down-regulate th e activation of STAT5 in primary CML cells. Curcumin may be used in treatment of leukemia.