三氧化二砷下调慢性髓系白血病骨髓细胞VEGF的表达

Down-regulation of Expression of Vascular Endothelial Growth Factor Induced by Arsenic Trioxide in Bone Marrow Cells of Chronic Myeloid Leukemia

为了研究三氧化二砷 (As2 O3 )对慢性髓系白血病 (CML)各期患者血管内皮生长因子 (VEGF)表达水平的影响 ,采用酶联免疫吸附法 (ELISA)检测正常人和CML慢性期、加速期和急变期患者骨髓细胞经As2 O3 作用前、后培养上清液VEGF水平的变化。结果发现 ,2 0例慢性期、8例加速期和 7例急变期患者骨髓细胞培养上清液VEGF水平分别为 6 4 9.16± 382 .2 0 pg/ml,5 6 0 .2 7± 4 0 9.14 pg/ml和 5 87.18± 4 15 .2 8pg/ml,明显高于对照组的15 2 .16± 15 0 .0 9pg/ml(P <0 .0 1) ,但不同病程阶段的CML患者间VEGF水平的差别无统计学意义。慢性期、加速期及急变期CML患者骨髓细胞经浓度为 5× 10 -6mol/L的As2 O3 处理 72小时后 ,VEGF表达水平均出现明显下调 ,分别为 396 .6 6± 2 5 7.4 7pg/ml,36 3.4 2± 2 39.85pg/ml和 4 0 7.4 7± 2 19.38pg/ml,与未加As2 O3 组比较差别显著 (P <0 0 5 )。结论 :VEGF异常增高可能在CML整个发病过程中都发挥一定作用 ,As2 O3

To investigate the effect of arsenic trioxide (As 2O 3) on vascular endothelial growth factor (VEGF) expression in different courses of chronic myeloid leukemia (CML), VEGF level was measured with ELISA in the cultural supernatants of bone marrow mononuclear cells from CML patients. The results showed that supernatants of cultured bone marrow cells from 35 CML patients (20 chronic, 8 accelerated and 7 blast crisis phases) contained significantly higher VEGF levels (649.16±382.20 pg/ml, 560.27±409.14 pg/ml and 587.18±415.28 pg/ml, respectively) than that in 15 normal control samples (152.16±150.09 pg/ml; P<0.01), but no significant differences were found in VEGF levels among different phases of CML. The bone marrow cells treated with As 2O 3 (5×10 -6 mol/L) for 72 hours resulted in significant reduction of VEGF levels (down to 396.66±257.47 pg/ml, 363.42±239.85 pg/ml and 407.47±219.38 pg/ml, respectively) (P<0.05). In conclusion, abnormal high expression of VEGF plays a role in the pathogenetic course of CML and it is probably an additional anticancer mechanism for As 2O 3 to inhibit VEGF expression of leukemic cells.