齐留通及塞来昔布对小鼠肿瘤组织血管内皮生长因子、基质金属蛋白酶2表达影响

Zileuton and celecoxib effect on expression of vascular endothelial growth factor and matrix metalloproteinase-2

目的观察本噻羟脲(齐留通)、塞来昔布单独及联合应用时对荷瘤小鼠肿瘤血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶2(matrix metalloproteinase,MMP-2)基因及蛋白表达的影响。方法用小鼠结肠癌CT26细胞建立荷瘤小鼠模型,应用反转录聚合酶链反应(RT-PCR)检测肿瘤组织中VEGF和MMP-2的基因表达;蛋白质印迹法(Western Blot)检测肿瘤组织中VEGF和MMP-2蛋白的表达。结果联合用药治疗组、塞来昔布治疗组和齐留通治疗组及相应的干预组VEGF和MMP-2基因、蛋白表达水平均低于其各自对照组(P<0.05),两组联合用药组与各单独应用塞来昔布及齐留通组相比VEGF、MMP-2的基因、蛋白表达水平降低(P<0.05)。联合用药、单独应用塞来昔布及齐留通3组干预组与各自治疗组相比VEGF、MMP-2的基因表达下降(P<0.05)。结论齐留通与塞来昔布都可以抑制肿瘤组织VEGF与MMP-2基因及蛋白的表达,且齐留通与塞来昔布各自的剂量减半联合应用抑制效果优于单用任意一种全剂量药物;无论联合用药还是单用任意一种药物,其干预组对VEGF、MMP-2的基因及蛋白表达的抑制作用均优于治疗组。

Objective To determine inhibitory effects of the combination of Zileuton and celecoxib or alone on vascular endothelial growth factor（VEGF） ,matrix metalloproteinase-2 （MMP-2） gene and protein expression. Methods Male mice were used to establish CT26 transplanted tumor models. The contents of gene of VEGF and MMP-2 were detected in tumor tissues with RT-PCR. The corltents of protein qf VEGF and MMP-2 were detected in tumor tissues with western-blot. Results The VEGF,MMP：2＂gene and protein expression in combining treatment group, celecoxib in treatment group and Zileuton in treatment group were significantly lower than those in control groups, and VEGF, MMP-2 gene and protein expression in combining treatment group were significantly lower than those of celecoxib in treatment group or Zileuton in treatment group; VEGF,MMP-2 gene and protein expression in combining intervention group,celecoxib in intervention group and Zileuton in intervention group were significantly lower than those in their treatment groups. Conclusion Both VEGF and MMP-2 gene and protein expression were suppressed by Zileuton or celecoxib,the effect of combination in half dose of the two drugs is better than that of the single drug. The effects of intervention groups are better than those of their respective treatment group.