CAJ | 학술논문

目的我们前期研究证实PPARγ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防治胃癌的机制.方法采用微阵列技术对罗格列酮体内干预的大鼠胃癌实验模型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.结果采用微阵列技术在大鼠胃癌组织中筛选出79个上调的差异表达基因,其中RSG处理组大鼠胃癌组织中DLK1基因表达显著高于MNNG诱癌组.同时我们检测MNNG诱癌组14例大鼠胃癌组织及癌旁组织中DLK1的mRNA水平,发现胃癌组织中DLK1表达明显低于癌旁组织.体外实验结果显示罗格列酮诱导AGS细胞PPARγ及DLKI的表达,并呈剂量依赖,PPARγ拮抗剂GW9662能阻断罗格列酮诱导DLK1表达的作用.结论罗格列酮通过PPARγ依赖途径诱导AGS胃癌细胞DLK1的表达,诱导DLK1表达可能是罗格列酮预防胃癌发生机制之一.
목적 아문전기연구증실PPARγ배체라격렬동(RSG)구유예방화학치암제N-갑기-N'-초기-아초기고(MNNG)유도대서위암발생적작용,본연구의탐토라격렬동방치위암적궤제.방법 채용미진렬기술대라격렬동체내간예적대서위암실험모형진행기인표체보적분석연구,사선PPARγ배체항종류신적파기인병여험증.결과 채용미진렬기술재대서위암조직중사선출79개상조적차이표체기인,기중RSG처리조대서위암조직중DLK1기인표체현저고우MNNG유암조.동시아문검측MNNG유암조14례대서위암조직급암방조직중DLK1적mRNA수평,발현위암조직중DLK1표체명현저우암방조직.체외실험결과 현시라격렬동유도AGS세포PPARγ급DLKI적표체,병정제량의뢰,PPARγ길항제GW9662능조단라격렬동유도DLK1표체적작용.결론 라격렬동통과PPARγ의뢰도경유도AGS위암세포DLK1적표체,유도DLK1표체가능시라격렬동예방위암발생궤제지일.
Objective Our previous study demonstrated that PPARγ, ligand resiglitazone prevents gastric carcinogen-esis in rats induced by chemical carcinogen N -methyl -N' -nitro -N -nitrasoguanidine (MNNG). We attempted to deter-minenovel anti - cancer mechanisms of rosiglitazone. Methods By examining the gene expression profiles of MNNG induced gastric cancer and the rosiglitazone treated gastric cancer with Uniset Rat Ⅰ Bioarray microarray. Results We identified a gene that showed prominent responses in rosiglitazone treated group. The delta like 1 homologue (DLK1) was significantly upregulated in rat gastric carcinoma of rosiglitazonetreated group when compared with the MNNG group. We further examined the DLK1 expression in rat gastric cancer of MNNG group and found that expression of DLK1 was down - regulated in rat gas-tric cancerous tissue compared with adjacent normal tissue. Rosiglitazone markedly induced the expression of DLK1 in AGS cell line. Pre - treatment with GW9662 markedly reduced rosiglitazone - induced DLK1 expression. Conclusions Upregula-tion of DLK1 may be one of the mechanisms underlying the ehemopreventive effect of resigltizaone in gastric cancer.