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  

Effect of Arsenic Trioxide on Related Factors of Angiogenesis in K562/A02 Cells

作　　者：陈牧[1] 张建东[1] 张育[1] 王晓铃[1] 沈维干[1] 李国青[1] 

机构地区：[1]江苏扬州大学医学院临床医学系诊断学教研室,225001

出　　处：《肿瘤防治研究》2007年第9期682-685,共4页Cancer Research on Prevention and Treatment

摘　　要：目的探讨三氧化二砷(arsenictrioxide,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,0.05μMAs2O3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(P>0.05),但在72h则对MMP-2、9的活性有明显抑制作用(P<0.05);0.4和3.2μMAs2O3可显著抑制细胞增殖,下调VEGF并使MMP-2、9活性减弱(P<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。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. Methods MTT 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. Results Neither the proliferation nor VEGF expression of K562/A02 cells was influenced by 0. 05 μM As2O3 after 24, 48 and 72 hours＇ incubation. The activities of MMP-2, 9 were not effected after 24, 48 hours＇ incubation with 0. 05 μM As203 （P〉0. 05）, but they were significantly inhibited after 72 hours （P〈0. 05）. 0. 4 and 3.2 μM As203 highly inhibited the proliferation, down regulated VEGF expression and inhibited the activity of MMP-2, 9 of K562/A02 cells （P〈0. 05）. Conclusion The 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.

关 键 词：三氧化二砷 血管内皮生长因子 基质金属蛋白酶 明胶酶谱 

分 类 号：R733.7[医药卫生—肿瘤]