信号素4D影响直肠癌裸鼠移植瘤的血管新生.pdf

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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