碘-125粒子照射人胃癌细胞株后的全基因组表达  

Global gene expression responses to Iodine-125 radiation in three human gastric cancer cell lines

作　　者：邹雷[1] 罗开元[2] 乔鸥[1] 许建彪[3] 

机构地区：[1]云南省第一人民医院肝胆外科,昆明650032 [2]云南省第一人民医院普外科,昆明650032 [3]云南省第二人民医院普外科

出　　处：《中华外科杂志》2014年第8期612-616,共5页Chinese Journal of Surgery

基　　金：云南省科技厅应用基础研究重点资助项目（2008CC）

摘　　要：目的 探讨胃癌细胞接受碘-125 （^125I）粒子照射后的基因表达变化.方法 用^125I粒子分别照射高分化（BGC-823）、中分化（AGS）以及低分化（NCI-N87）人胃癌细胞株.每个细胞株分为实验组（接受100 cGy^125I粒子照射）和对照组（不接受照射）.应用微阵列芯片检测3株细胞株被照射后全基因表达变化情况,设定检验水准（P＜0.05及表达倍数变化大于2）以筛选差异表达的基因.应用实时定量（qRT）-PCR验证差异基因表达情况,应用BisoGenet重建蛋白-蛋白相互作用网络,用Cytoscape复杂网络分析和形象化平台进行基因网络关系分析.应用DAVID进行GO及KEGG通路分析.结果 高、中、低3个不同分化细胞株经相同剂量率的^125I粒子照射后,基因芯片的层次聚类分析结果显示,3株胃癌细胞株的对照组和实验组从细胞聚类分析上看是属于同一聚类,NCI-N87细胞经^125I粒子照射后,有895个基因表达上调,786个基因表达下调;AGS细胞经^125I粒子照射后,有124个基因表达上调,161个基因表达下调;BGC-823细胞经^125I粒子照射后,有2 412个基因表达上调,3 243个基因表达下调.电离辐射后会引起非常复杂的转录调控变化,KEGG通路分析说明这些差异表达基因在特定的细胞通路中有重叠.经qRT-PCR验证其中具有相似动力学特性的差异表达基因TRAF3IP2-AS1、SDC1、RABL2B和NOM1 4个基因,与对照组相比均出现了差异表达（P＜0.05）.结论 ^125I粒子照射胃癌细胞株后会导致较多基因表达上调或下调,其中TRAF3IP2-AS1、SDC1、RABL2B和NOM1在3株细胞株均发生显著变化,推测可能是^125I粒子治疗胃癌的作用点,为将来研制治疗胃癌靶向药物提供参考.Objective To study genome-wide gene expression changes in gastric cancer cells after iodine-125 （125 I） particle irradiation.Methods ^125I particles were used to irradiate three gastric cancer cell lines of various differentiation levels：high （BGC-823）,medium （AGS） and low （NCI-N87）.Whole-genome gene expression was investigated with microarray.The gene expression in iodine-125 irradiated and untreated cancer cells was compared,and the genes with transcript levels altered for at least 2 folds （P 〈 0.05） were selected.The change in gene expression levels was verified by using quantitative real-time （qRT）-PCR.Results The three gastric cancer cell lines received the same dose rate of ^125I particle irradiation.Cluster analysis showed that the Gene Ontology（GO） categories did not change in the three cell lines,but changes in gene expression levels were evident for many genes.After ^125I particle irradiate NCI-N87 cells,895 genes were up-regulated,786 genes were down-regulated; AGS was irradiated by ^125I seed,there were 124 genes upregulated,161 genes were down-regulated; BGC-823 cells were treated by ^125I seed irradiation,2 412 genes upregulated,3 243 downregulated genes.After ionizing radiation can cause very complex transcriptional regulation changes,KEGG pathway analysis shows that these differentially expressed genes overlap in a particular cell pathway.Four genes,TRAF3IP2-AS1,SDC1,RABL2B and NOM,were found having at least 2-fold difference in expression （P 〈 0.05）,and the gene expression alteration was confirmed by qRT-PCR.Conclusions ^125I particle irradiation caused gene expression changes in gastric cancer cells.The expressions of TRAF3IP2-AS1,SDC1,RABL2B and NOM are altered significantly in all three cell lines studied,indicating that these genes may play an important role in the ^125I seed treatment of gastric cancer.These genes could be potential targets for developing anti-cancer drugs in the future.

关 键 词：胃肿瘤 体外研究 近距离放射疗法 碘放射性同位素 基因表达 

分 类 号：R735.2[医药卫生—肿瘤]