罗格列酮通过下调环氧化酶-2、血管内皮生长因子的表达预防MNNG诱导大鼠胃癌发生  

Rosiglitazone suppresses gastric carcinogenesis in rats by downregulating COX -2 and VEGF expression

作　　者：陈白莉[1] 柯春龙[1] 何瑶[1] 贺青[1] 聂小英[1] 廖山婴[1] 

机构地区：[1]中山大学附属第一医院,广州510080

出　　处：《中国实用医刊》2009年第10期1-4,共4页Chinese Journal of Practical Medicine

基　　金：广东省医学科研基金（A2008175）

摘　　要：目的研究证实过氧化酶体增殖因子活化受体γ（PPAR-γ）配体罗格列酮（RSG）具有预防化学致癌剂N-甲基-N’-硝基-亚硝基胍（MNNG）诱导大鼠胃癌发生的作用，本研究拟探讨罗格列酮预防大鼠胃癌形成的可能机制。方法采用RT—PCR及免疫组化法检测罗格列酮处理后大鼠胃癌组织环氧化酶-2（COX-2）、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）mRNA及蛋白的表达。结果MNNG诱癌组14例大鼠胃癌组织VEGF、COX-2mRNA的表达明显高于癌旁组织（P〈0．01），而MMP-9的表达在大鼠胃癌及癌旁组织中差异无统计学意义（P〉0．05），RSG处理组（15例）大鼠胃癌组织VEGF、COX-2mRNA的表达明显低于MNNG诱癌组大鼠胃癌组织，免疫组化显示MNNG诱癌组大鼠胃癌组织COX-2阳性物质主要分布在癌细胞胞浆或沿核膜周边，在间质的血管内皮细胞、成纤维细胞及单核细胞中亦可见阳性表达；VEGF阳性细胞主要位于癌细胞胞浆内，血管内皮细胞也有阳性表达。罗格列酮处理后大鼠胃癌组织的COX-2阳性细胞分布与MNNG诱癌组胃癌组织相似，而VEGF阳性细胞主要位于癌细胞胞浆内，血管内皮细胞未见明显VEGF表达。结论罗格列酮可下调大鼠胃癌组织COX-2及VEGF的表达，促进肿瘤细胞凋亡、减少肿瘤血管生成可能是罗格列酮预防大鼠胃癌发生的机制之一。Objective To demonstrat that PPARγ ligand rosiglitazone prevents gastric carcinogenesis in rats induced by chemical carcinogen N - methyl - N＇ - nitro - N - nitrosoguanidine （MNNG）. We attempted to determincpossible anti - cancer mechanisms of rosiglitazone. Methods By examining COX- 2, VEGF and MMP- 9 expression in MNNG induced gastric cancer and the rosiglitazone treated gastric cancer with RT - PCR and immunohistochemistry. Results The COX - 2 and VEGF mRNA was significantly lower in rat gastric carcinoma of rosiglitazone treated group when compared with the MNNG group. Similarly, COX - 2 immunoreactivity was mainly detected in the perinuclear and cytoplasm of carcinoma cells. Expression of COX - 2 was also observed in vascular endothelial cells, fibroblasts and inflammatory mononuclear cells in the tumor stroma. Cytoplasmic staining for VEGF was mainly seen in the tumor cells and vascular endothelial cells, whereas COX - 2 immunostain was lower and loss of VEGF expression in vascular endothelial cell was observed in rat gastric carcinoma of rosiglitazonetreated group by immunohistochemistry. Conclusions Downregulation of COX -2 and VEGF may be one of the mechanisms underlying the chemopreventive effect of rosigltizaone in gastric cancer.

关 键 词：过氧化酶体增殖因子活化受体γ 胃癌 大鼠模型 环氧化酶-2 血管内生长因子 

分 类 号：R735[医药卫生—肿瘤]