PPARγ配体罗格列酮预防MNNG诱导的大鼠胃癌发生的实验研究  

Effects of rosiglitazone,a PPARγ ligand,on chemoprevention of MNNG-induced gastric cancer in rats

作　　者：陈白莉[1] 廖山婴[1] 曾志荣[1] 梁伟强[2] 于君[2] 朱伟杰[2] 胡品津[1] 

机构地区：[1]中山大学附属第一医院消化内科,广东广州510080 [2]香港中文大学消化疾病研究所及李嘉诚健康科学研究所

出　　处：《中国病理生理杂志》2009年第8期1522-1527,共6页Chinese Journal of Pathophysiology

基　　金：广东省医学科研基金资助项目(No.A2008175)

摘　　要：目的:探讨PPARγ配体罗格列酮(RSG)对化学致癌剂N-甲基-N’-硝基-亚硝基胍(MNNG)诱导的大鼠胃癌发生的影响,并探讨罗格列酮防治胃癌的可能机制。方法:二级Wistar大鼠90只,随机分为5组:A组(对照组),B组(MNNG诱癌组),C-E组(RSG处理组,分别灌喂不同浓度罗格列酮),以上处理连续10个月,比较各组动物胃癌发生率的差异。同时采用微阵列技术对罗格列酮体内干预的大鼠腺胃癌进行基因表达谱的分析研究,筛选PPARγ配体抗肿瘤新的靶基因并予验证。结果:A、B、C、D、E组动物胃癌的发生率分别为0%(0/10)、70%(14/20)、15%(3/20)、30%(6/20)和30%(6/20),病理组织学证实为腺癌。与B组相比,C、D、E组动物腺胃癌的发生率均明显低于B组动物(P<0.01)。采用微阵列技术在大鼠腺胃癌组织中筛选出79个上调的差异表达基因,其中RSG处理组大鼠胃癌组织中HCaRG基因表达显著高于MNNG诱癌组,同时应用荧光定量PCR证实在RSG处理组其它大鼠胃癌组织中HCaRG表达明显高于MNNG诱癌组(P<0.05),而在人胃癌组织中HCaRG表达明显低于正常胃黏膜组织(P<0.05)。结论:PPARγ配体罗格列酮能显著降低MNNG诱导的大鼠腺胃癌发生率,诱导HCaRG表达可能是罗格列酮预防胃癌发生机制之一。AIM： To examine the chemo- preventive effects of peroxisome proliferator-activated receptor γ. （PPARγ） ligand rosiglitazone （RSG） on a rat model of gastric carcinogenesis induced by chemical carcinogen N- methyl -N＇ -nitro- N-nitrosoguanidine （MNNG）. We also attempted to identify novel anticancer mechanisms of rosiglitazone. METHODS： Ninety male Wistar rats were randomly allocated into six groups ： group A （ control group） ; group B （MNNG group）; group C, D and E （RSG group, given different concentrations of rosiglitazone）. The treatment procedures were terminated at 40th week. Stomach was harvested and gastric carcinoma was verified by histology. The gastric cancer incidence in different groups was calculated. To elucidate the mechanisms underlying the chemo - preventive effects of PPARγ ligand, we examine the gene expression profiles of MNNG induced gastric cancer and the rosiglitazone treated gastric cancer with Uniset Rat I Bioarray microarray. RESULTS： Incidence of gastric cancer in group A -E was 0% （0/ 10）, 70% （14/20）, 15% （3/20）, 30% （6/20）and 30% （6/20）, respectively. Gastric cancer incidence in group C, D and E was significantly lower than that in group B （P 〈 0.01 ）. A gene that showed prominent responses in rosiglitazone treated group was identified. The hypertension- related, calcium -regulated gene （HCaRG） was significantly upregulated in rat gastric carcinoma in rosiglitazone treated group when compared to MNNG group. The expression of HCaRG was down - regulated in human gastric cancerous tissue. CONCLUSION ： PPARγ ligand rosiglitazone has a potent chemo - preventive effect against gastric cancer development in rats. Upregulation of HCaRG may be one of the mechanisms underlying the chemo - preventive effect of rosiglitazone in gastric cancer.

关 键 词：过氧化物酶增殖激活受体γ 罗格列酮 胃肿瘤 基因 HCaRG 

分 类 号：R735.2[医药卫生—肿瘤]