claudin-7基因敲除对裸鼠结肠癌肝转移模型中的致癌作用

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1、Claudin-7基因敲除对裸鼠结肠癌肝转移模型中的致癌作用赵雪峰刘福全张晓微(大连大学附属新华医院胃肠微创外科中心辽宁大连116021)【摘要】目的：研宄Claudin-7基因敲除对裸鼠结肠癌肝转移模型中的致癌作用及其前临床意义。方法：釆用Claudin-7基因敲除及基因重组质粒pcDNA6-Claudin-7基因敲除转染的HT29结肠癌细胞建立裸鼠结肠癌肝转移模型，随机分为2组，即Claudin-7敲除组和对照组。制模60天后比较两组间转移瘤形成情况，并采用免疫组织化学检测两组肝转移组织的Claudin-7表达程度。结果：Claudi

2、n-7敲除组肝质量、肝转移评分、淋巴结转移发生率、血性腹水成率、腹膜种植转移发生率、远处转移发生率明显高于对照组，两组间差异有统计学意义(p<0.05)。肝转移的组织病理学检测中，发现Claudin-7表达在两组间有显著差异，并有统计学意义(p<0.05)。生命表证实，Claudin-7敲除组生存率明显低于对照组，差异有统计学意义(p<0.01)。结论：Claudin-7基因敲除可促进裸鼠结肠癌肝转移的形成，况且Claudin-7表达可作为肿瘤转移的评价指标。【关键词】Claudin-7基因敲除裸鼠结肠癌肝转移【中图分类

3、号】R446.5【文献标识码】A【文章编号】1672-5085(2014)03-0034-03【Abstract】Objective:TostudythecarcinogeniceffectsofClaudin-7geneknockdownonthelivermetastasisofcoloncancer(LMCC)nudemicemodel(NMM)anditspreclinicalresearch.Methods:After60daysofthespleeninjection,HT29coloncancercellstransfect

4、edbyrecombinantclonevectorpcDNA6-Claudin-7geneknockdownwereusedtoestablishtheLMCC-NMM.Thetumorbearingnudemicewererandomizedinto2groups,Claudin-7knockdowngroupandScramblecontrolgroup.Inaddition,Claudin-7knockdowngroupwascancercellsinjectedintospleentostudygroupandcontrolgr

5、oup,evaluatingmetastatictumorformation,livermetastasistissueswereinvestigatedexpressionofClaudin-7proteinviaimmunohistochemistry.Results:Theliverweight,livermetastasisscores,lymphnodemetastasisrate,bloodyascitesrate,peritonealseedingrate,anddistantmetastasisrateofClaudin-

6、7knockdowngroupweresignificantlygreaterthanthatinthecontrolgroup(p<0.05).ExpressionofClaudin-7proteinwasmarkedhistopathologicaldifferenceoflivermetastasistissuesbetweenClaudin-7knockdowngroupandcontrolgroup，anddifferencewasstatisticallysignificant(p<O.O5).Livetables

7、showedthatClaudin-7knockdowngroupisinverselycorrelatedwithcumulativesurvivalofLMCC-NMM(p<O.Ol).Conclusion:Claudin-7geneknockdownmaybepromotetheformationofLMCC-NMM,andexpressionofClaudin-7asanevaluatingindexfortumormetastasis【Keywords】Claudin-7;Geneknockdown;Nudemice;Co

8、loncancer;LivermetastasisClaudins是构成细胞紧密连接的骨架蛋白，其异常表达与肿瘤浸润和转移冇关［1】。其中，Claudin-7是Claudins多基因家族中的重