中文摘要：

目的对比As2O3不同干预方式对白血病细胞株NB4的侵袭力和基质金属蛋白酶2，9（MMP-2、MMP-9）活性的影响。方法噻唑蓝（MTT）法检测As2O3恒定和变化两种体系体外干预对NB4细胞的增殖抑制，ELISA检测2种体系中处理的NB4细胞的MMP-2和MMP-9蛋白含量的变化。明胶酶谱法检测2种As2O3处理前后NB4细胞MMP-2活性变化，Westen blot检测活性MMP-9蛋白表达，Transwell小室穿透实验检测两种As203处理方式对NB4细胞穿透力的影响。结果①与平行对照组比较0．1μmol·L^-1As2O3恒定浓度体系中持续作用72h，对MMP-2、MMP-9的活性和NB4细胞侵袭力影响不显著,0．5μmol·L～As2O3持续作用24h与对照组比较无明显差异，48h以后MMP-2、MMP-9的活性和NB4侵袭力降低，与对照组比较差异显著。1．0μmol·L^-1以上浓度As203处理24h，MMP．2、MMP．9活性和NB4细胞侵袭力下降，并呈时间依赖性。②2．0μmol·L～As2O3恒定浓度体系与峰浓度为5．0μmol·L^-1，终质量浓度为0μmol·L^-1的变化浓度体系比较，前者对NB4的侵袭力和MMPs活性的抑制程度比后者更显著。结论NB4细胞的侵袭力与其MMP-2、MMP-9活性有关，促分化有效的低浓度As2O3对NB4细胞侵袭力和MMP-2、MMP-9活性抑制作用不明显。在干预时间相同的情况下，促凋亡有效的恒定浓度As203持续作用，对NB4细胞侵袭力和MMP-2、MMP-9活性的抑制强度大于峰浓度很高但持续时间很短的变化浓度体系，这可能是临床上As2O3持续缓慢输注法较常规给药法更能有效降低急性早幼粒细胞白血病（APL）中枢神经系统浸润和早期的致死性脑出血发生率的机制之一。

英文摘要：

OBJECTIVE To compare the influence of two kinds arsenic trioxide （As203） treatment on activity of MMPs and cell invasion in NB4 cells. METHODS NB4 cell line were treated with steady and changing concentrations of AS203 in vitro respectively. The cell death was investigated by MTT assay. The activities of MMPs were detected by enzyme-linked immunosorbent assay, and their expressions were measured by western blotting and gelatinase zymography. The migration capabilities of NB4 at baseline and after being treated with the two kinds of different As2O3 treatment were evaluated by transwell assay. RESULTS ① With As2O3 continuous treatment in steady concentration： the MMPs activity and migration of NB4 cells were not significantly decreased by 0.1 μmol·L^-1 As2O3 for 72 h. The activity was remarkably inhibited by As2O3 in 0.5 for 72 h, in 1.0 μmol·L^-1 for 48 h and in 2.0 μmol·L^-1 and above 24 h compared with the parallel control. ②The inhibition effects of As2O3 on MMPs activity and migration of NB4 with As203 in 2.0 μmol·L^-1 steady concentration treatment were remarkable compared with that in changing concentration treatment in vitro, even though the peak of As2O3 concentration was 5.0 μmol·L^-1. CONCLUSION As2O3 with lower concentration could not inhibit MMPs activity and invasion of NB4 effectively, however, As203 at higher apoptosis effective concentration decreased the MMPs activity and inhibited NB4 invasion remarkably in a concentration- and time-dependent manner. The inhibition efficiency of As2O3 on MMPs activity and NB4 cell invasion treated with general speed As203, which has a fluctuated serum arsenic and a long pause of apoptosis non-effective lower arsenical level in serum between the two dosages of As203 administration, was less than that treated with the slow-steady speed As203 infusion, which can keep a relatively constant promoting apoptosis effective level of serum arsenic during the whole As203 infusion treatment.