三氧化二砷对阿霉素耐药的白血病细胞血管新生相关因子的影响.docVIP

三氧化二砷对阿霉素耐药的白血病细胞血管新生相关因子的影响 nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; 作者：陈牧 张建东 张育 王晓铃 沈维干 李国青 【摘要】nbsp; 目的探讨三氧化二砷(arsenic trioxide, As2O3)对白血病耐药细胞株K562/A02细胞血管新生相关因子血管内皮生长因子（VEGF）表达水平及基质金属蛋白酶2、9（MMP2、9）活性的影响。 方法用噻唑蓝法(MTT)测定As2O3对K562/A02细胞的增殖抑制作用，用酶联免疫吸附试验测定细胞上清中VEGF含量，用明胶酶谱法半定量测定细胞上清中MMP2、9的活性。 结果K562/A02细胞的IC50是（1.64±0.16）μM，0.05μM As2O3对细胞增殖和VEGF的表达没有明显影响，对MMP2、9的活性在24、48h无明显影响(Pgt;0.05)，但在72h则对MMP2、9的活性有明显抑制作用(Plt;0.05)；0.4和3.2μM As2O3可显著抑制细胞增殖，下调VEGF并使MMP2、9活性减弱(Plt;0.05)。结论As2O3可能通过下调VEGF的表达和抑制MMP2、9活性而发挥抗白血病细胞血管新生作用。 【关键词】nbsp; 三氧化二砷； 血管内皮生长因子； 基质金属蛋白酶； 明胶酶谱 　　Effect of Arsenic Trioxide on Relatednbsp; Factors of Angiogenesis in K562/A02 Cells 　　Abstract：Objective To investigate the effect of arsenic trioxide (As2O3) on the expression of VEGF and the activity of MMP2 and 9 in K562/A02 cells. MethodsMTT assay was used to detect the inhibition ratio of K562/A02 cell. Enzymelinked immunosorbent assay (ELISA) was used to detect the level of VEGF. Gelatin zymography assay was used to assess the activity of MMP2, 9. ResultsNeither the proliferation nor VEGF expression of K562/A02 cells was influenced by 0.05μMnbsp; As2O3 after 24, 48 and 72 hours’ incubation. The activitiesnbsp;nbsp; ofnbsp;nbsp; MMP2, 9 were not effected after 24, 48 hours’ incubation with 0.05μM As2O3 (Pgt;0.05),nbsp; but they were significantly inhibited after 72 hours (Plt;0.05). 0.4 and 3.2μMnbsp; As2O3 highly inhibited the proliferation, down regulated VEGF expression and inhibited the activity of MMP2, 9 of K562/A02 cells (Plt;0.05). ConclusionThe possible mechanism of antileukemic angiogenesis by As2O3 may be achieved by inhibiting the expression of VEGF and the activity of MMP2 and 9. 　　Key words：Arsenic trioxide;VEGF; MMP;Gelatin zymography assay 　　0引言 　　肿瘤细胞的多药耐药(Multidrug resistance,nbsp; MDR)是导致临床白血病患者化疗失败的常见原因。 造成肿瘤细胞MDR的因素众多， 其中血管新生(Angiogenesis)与肿瘤多药耐药的关系正逐渐受到越来越多的重视。 肿瘤血管新生不仅是白血病发生、 发展和浸润的