Stat3显性负性基因调控人结肠癌细胞增殖与凋亡的分子机制

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1、•662•屮华冷通外科杂志2006年9丿J第21卷第9期ChmjGrnSurg,SeMmbm2006,Vol.21.W・9・论著・Stat3显性负性基因调控人结肠癌细胞增殖与凋亡的分子机制赵勇王杉叶颖江周赫姜可伟崔志荣【摘要】目的探讨转染Siat3(转录仃。传导子和激活子3)城性负性荃因Stat3p质粒阻断人结肠癌细胞系SW480细胞的Slai3信号传£通路対人结肠癌细胞增旳和凋亡的影响及町能的机制。方法应用阳离子脂质体向人结肠癌细胞系SW480细胞中转染携带Slat3p垄因的质粒，四畔盐法检测细胞增殖能力，流式细胞术检测细胞周期和细胞凋亡，反转录聚

2、合胡链反应检测Slat3杷廉冈cyclin1)1Jxd-xLmRNA达悄况。数据统计分析采用独立样本f检验。结果转染血恥质粒36h后,SW480细胞的増殖受到显杆抑制(r=5.216,^=0.006)；G0/GI期的细胞比例由40.37%上升至67.25%,S期细胞山44.68%F降至31.23%;发生早期凋亡的细胞比例由5.34%匕升至24.42%；同时cyclin1)1%bcl-x,mRNA表达水平较对照组显著下降(f=5.228,P=0.010;/=3.517,P=0.025)0结论转染携WStat3p肚冈的质粒町以通过下调Slal3靶肚因的衣

3、达抑制人结肠癌细胞的增殖，促进凋亡，为以Stat3为靶点的结肠癌丛因治疗提供了实验垄础。【关键词】结肠肿卿；细胞增殖；细胞凋亡；转录因子,Slal3；显性负性MolecularmechanismsinvolvedinregulationofproliferationandapoptosisbyStat3dominantnegativegeneincoloncancercellsZHAOYong.WANCShan.YEYing-jiang,ZHOUJing,JIANGKe-wei,CUIZhi-rong.DepartmentofGastroenter

4、ologicalSurgfryandSurgicalOncology/laboratorytPekingUniversityPeople'sHospital,Beijing100044.ChinaCorrespondingauthor：WANGShantE-mail：shwang^0@263.net[Abstract]ObjectiveTostudytheinfluenceoftransferringadominant・neg8liveStat3gene,Stat3poncoloncancercells1proliferationandapoptos

5、isinvitro・MethodsCellcultureofhumancoloncancercelllineSW480andtransienttransfectionwereusedtoevaluatetheefleetoftransferringStal3

6、Jtocancercells.CellproliferationtcellcycleandapoptosiswerequantifiedbyMTTandflowcytometrytrespectively.ThemRNAexpressionofStat31stargetgenecyclinDIa

7、ndbcl-xLwasdetectedbyreversetranscriptionpolymerasechainreaction・Independenlttestswereusedfordatastatistics・Results36hafterS

8、yapoptosiscellsincreasedfrom5.34%to24.42%；mRNAexpressionofcyclinDIandbcl-x(declinedsignificantly(t=5.288,P=0.010；/=3.517.P=0.025).ConclusionBlockingStat3signalingpathwaybytransfectionofStat3pplasmidinhibitstheproliferationandpromotesapoptosisofcoloncancercells,whichprovidesaexp

9、erimentalfoundationofSta6targetedcoloncancergenetherap