三氧化二砷对K562细胞血管内皮生长因子及受体和MMP-2、9的影响

目的探讨三氧化二砷（As2O3）对K562细胞的血管内皮生长因子（VEGF）及其受体（VEGFR）表达水平和基质金属蛋白酶2、9（MMP-2、9）活性的影响。方法用MTT法测定As2O3对K562细胞的毒性，酶联免疫吸附试验测定细胞上清中VEGF含量，流式细胞术检测细胞的VEGFR表达率，明胶酶谱法半定量测定细胞上清中MMP-2、9的活性。结果①Mar法检测K562细胞的，IC50为（2．12±0．11）μmol／L，0．4～6．4μmol／LAs2O3可显著抑制K562细胞的增殖（P＜0．05）。②0．05μmol／L As2O3对VEGF无明显影响（P＞0．05）；0．4和3．2μmol／LAs2O3可明显下调VEGF表达（P＜0．05）；As2O3对VEGFR的表达无明显影响（P＞0．05）。③MMP-2、9经0．05μmol／L As2O3处理72h、0．4和3．2μmol／L As2O3处理24、48和72h均可显著抑制K562细胞MMP-2、9的活性（P＜0．05），这种抑制作用随As2O3浓度增加和作用时间延长而逐渐增强。结论As2O3可下调K562细胞VEGF的表达和抑制MMP-2、9的活性。

Effect of arsenic trioxide on VEGF/R and MMP-2, 9 expressed in K562 cells

OBJECTIVE: To explore the effect of arsenic trioxide (As2 O3) on the level of VEGF, VEGFR and the activity of MMP-2, 9 in K562 cells. METHODS: The inhibition ratio of K562 cell was detected by MTT assay, the level of VEGF by Enzyme-linked immunosorbent assay (ELISA), the expression ratio of VEGFR by flow cytometry (FCM), and the activity of MMP-2, 9 by gelatin zymography assay. RESULTS: (1) The IC50 of K562 cells was (2.12 +/- 0.11) micromol/L. Proliferation of K562 cells was significantly inhibited at the concentration of 0.4 - 6.4 micromol/L As2 O3 (P < 0.05). (2) The expression of VEGF was slightly up-regulated by 0.05 micromol/L As2 O3 (P > 0.05) and prominently inhibited by 0.4 micromol/L and 3.2 micromol/L As2 O3 (P < 0.05). As2 O3 had no influence on VEGFR. (3) The activity of MMP-2 and 9 was partly inhibited by 0.05 micromol/L As2 O3 incubated 72 hours and by 0.4, 3.2 micromol/L, As2 O3. With the increase of As2 O3 concentration and the incubation time, the inhibited effect on MMP-2 and 9 was enhanced. CONCLUSIONS: As2 O3 may down-regulate the expression of VEGF and inhibit the activity of MMP-2 and 9.