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时间:2020-04-30
《信号素4D影响直肠癌裸鼠移植瘤的血管新生.pdf》由会员上传分享,免费在线阅读,更多相关内容在行业资料-天天文库。
1、旦_lI中瘤麈20!第41卷第14期ChinJClinOncol2014,Vo1.41,No.14www.cjco.cn885基础研究·信号素4D影响直肠癌裸鼠移植瘤的血管新生冰丁晓洁①②李多①②黄新伟①②付娟娟①②潘王月①②陈俊英①②孙强明①②摘要目的:本文利用慢病毒介导的RNA干扰,在结直肠癌裸鼠皮下移植瘤模型中研究信号素4D(Sema4D)对血管新生的影响。方法:包装制备对照慢病毒和Sema4DshRNA干扰慢病毒,感染直肠癌细胞HCT一116。Transwe11迁移实验检测对照组和干扰组诱导内皮细胞迁移的能力。对照组和干扰组分别接种于裸鼠双侧腋窝皮下
2、。观察记录肿瘤生长,收获移植瘤做免疫组化和免疫荧光检测。结果:研究发现干扰Sema4D的表达能减弱癌细胞诱导内皮细胞迁移的能力,显著减缓移植瘤生长速度并降低瘤内血管密度。结论:由于Sema4D在诱导血管新生中的作用,干扰其信号通路将可能通过抑制血管新生来阻止肿瘤生长或转移,因此Sema4D有可能成为肿瘤抗血管新生疗法中有价值的治疗靶点。关键词结直肠癌信号素4D血管新生移植瘤模型RNA干扰doi:10.3969~.issn.1000—8179.20140314Sema4Ddeficiencyreducescolorectalcarcinomaxenograft
3、growthandvascularityinnudemiceXiaojieDING,DuoLI,XinweiHUANG,JuanjuanFU,YuePAN,JunyingCHEN,QiangmingSUN'C0rrespondenceto:QiangmingSUN;E—mail:msun08@yahoo.comMolecularEpidemiologyJointLaboratory,InstituteofMedicalBiology,ChineseAcademyofMedicalScience&PekingUnionMedicalCollege,Kunmin
4、g650118,China;YunnanKeyLaboratoryofVaccineResearch&DevelopmentonSevereInfectionsDiseases,Kunming650118,ChinaThisstudywassupposedbytheNationalNaturalScienceFoundationofChina(No.81171946),theSpecialResearchFundsfortheDoctoralProgramofHigherEducationofChina(No.20111106120055),andtheSc
5、ientificResearchFoundationforReturnedOverseasChineseScholars,MinistryofEducationofChina[No.(2011)1568】AbstractObjective:Semaphorin4D(Sema4D)actsasaregulatorforaxonguidanceincentralnervoussystemdevelopment.However,newevidenceindicatesthatSema4Dhasapreviouslyunrecognizedfunction,name
6、ly,compensatoryangiogenicfactor.ThisstudyaimedtoinvestigatetheefectofSema4Dontumorgrowthandvascularityofcolorectalcarcinoma(CRC)innudemice.Meth-ods:Sema4DwasknockeddowninCRCcellsbyinfectingthecellswithlentivirusescodingforSema4DshRNA.Twogroupsofcells,namely,thoseinfectedwithcontrol
7、virusesandthoseinfectedwithSema4DshRNAviruses,weresubjectedtomigrationassaytotesttheirabilityinduceendothelialcellmigration.Thetwocellgroupsweresubcutaneouslyinjectedintonudemice.Tumorgrowthwasdocumented.andthetumorsharvestedfromthemiceweresubjectedtoimmunohistochemistryorimmunoflu
8、orescenceanalyses.Re—suits
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