shugoshin1在非小细胞肺癌多西紫杉醇耐药中的作用及机制研究

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1、第四军医大学硕士学位论文1.SGO1高表达与非小细胞肺癌细胞对多西紫杉醇的耐药密切相关。2.成功建立SGO1上调非小细胞肺癌细胞株，其通过抑制促凋亡分子Bax的表达，增强抑制凋亡分子Bcl-2的表达来降低化疗药物诱导的细胞凋亡，通过减少G2/M期阻滞，增加P-gp蛋白表达这些途径降低细胞对多西紫杉醇的敏感性。3.成功建立SGO1下调非小细胞肺癌细胞株，其通过上调促凋亡分子Bax的表达，下调抑制凋亡分子Bcl-2的表达来增加化疗药物诱导的细胞凋亡，通过增加细胞G2/M期阻滞，下调P-gp蛋白表达这些途径增加细胞对多西紫杉醇的敏感性。4第四军医大学硕士学位论文TheRo

2、leandMolecularMechanismsofShugoshin1mediatedDocetaxelResistanceinNon-small-celllungCancerCandidateformaster:LiuJiayuSupervisor:ZhangHelongTutor:LiuLiliDepartmentofOncology,TangDuHospital,FourthMilitaryMedicalUniversity,Xi’an710038,ChinaAbstractKeywords：SGO1;NSCLC;DocetaxelresistanceInc

3、reasesinlungcancermaynumericallydominateoverallcancermortalitytrendsintheworld.Morethanonehalfofnon-small-celllungcancer(NSCLC)patientshaveadvanceddiseaseatdiagnosisandarebeyondthelimitsofsurgery.Howeveranumberofrandomizedclinicaltrialsandrecentmeta-analyseshavedemonstratedthatsurvival

4、inpatientswithadvancedstageⅢorstageⅣNSCLCcanbeprolongedwithchemotherapy.SeveralnewchemotherapeuticagentshaverecentlyshownencouragingactivityinNSCLC,especiallydocetaxel.However,manypatientsdevelopresistancewhichimpairsthesuccessofchemotherapy.Therehavebeenmanyspecificmechanismscontribut

5、ingtothedocetaxelresistancesuchastheoverexpressionofP-gpandMRP；mutationofeitherαorβsubunitofmicrotubulesandtheaberrationsoftheapoptoticpathwaysandtheDNArepairsystems,whichallfailedtoelucidatethedocetaxelresistacecompletely.SGO1isanewtumor-relatedmoleculewhichwasselectedfromtheCellomics

6、Arraysplatform.WehaveconfirmedthatSGO1playsanimportantroleinNSCLCbyaffectingtheG2/Mperiodof5第四军医大学硕士学位论文mitosiswhichisactuallyalsotheperiodwherethedocetaxelinducescancercellstoapoptosis.ConsideringtherehasbeennotanyreportontherelationshipbetweenSGO1anddocetaxelresistance,wethinkitisimp

7、ortantforustofurtherexplorethespecificfunctionofSGO1indocetaxelresistanceinNSCLC.Adocetaxel-resistantcellsublineA549/Taxoterederivedfromtheparental-sensitivecelllineA549wasestablishedbystepwiseselectionindocetaxeltostudytheexpressionofSGO1inresistantcelllines,thenweinvestigatetherole