三氧化二砷对白血病耐药细胞株细胞基质金属蛋白酶2、9活性的作用

Effect of arsenic trioxide on MMP-2,9 expressed in K562/A02 cell

目的:探讨三氧化二砷(arsen ic trioxide,ATO)对白血病耐药细胞株K562/A02细胞表达的基质金属蛋白酶2,9(MMP-2、9)活性的影响。方法:用MTT法检测不同浓度ATO对K562/A02细胞的增殖抑制率;用明胶酶谱法检测ATO对K562/A02细胞MMP-2、9活性的影响。结果:K562/A02细胞的MMP-2、9活性条带在对照组以MMP-2(72KD)最宽,MMP-9次之,MMP-2(62KD)最窄。MMP-2、9经0.05μMATO处理后在24、48小时与对照组比较无明显差异(P>0.05),72小时差异才具有显著性(P<0.05)。MMP-2、9的活性经0.4μM和3.2μM的ATO处理后随作用时间延长而抑制作用也逐渐增强,与对照组比较差异均有显著性(P<0.05)。结论:ATO可以有效抑制K562/A02细胞的MMP-2、9的活性,但其作用的强度与剂量及作用时间有关。ATO对MMP-2、9的活性的抑制可能是其抗白血病细胞血管新生的机制之一。

Objective ：To investigate the effect of the expression of the activity of MMP- 2, 9 in multidrug resistant leukemic cell K.562/A02 treated by arsenic trioxide （ATO）. Methods： The growth inhibitory activity of different concentrations of ATO in K562/A02 cell was detected by MTT assay. The activity of MMP- 2, 9 expressed by K562/A02 cells was assessed by gelatin zymography assay. Results： K562/A02 cells expressed both MMP -2 and MMP-9. Among MMP-2（72KD）, MMP-2（62KD） and MMP-9 in the control group, the electrophoresis strip of MMP-2 （72KD） was the widest. After seeded 72h, the activity of MMP-2 was inhibited by 0.05μM ATO （P〈0.05）. With the increase Of ATO incubation time, the inhibited effect was reinforced by 0.4 and 3.2μM ATO. Conclusion： ATO can inhibit the expression of the activity of MMP-2, 9, but it is influenced by the dose and time. One of the possible mechanisms of anti-leukemic angiogenesis by ATO may be achieved by inhibiting the expression of MMP-2, 9.