importazole和fenretinide对骨髓瘤细胞生物学特性的影响与其机制研究

《importazole和fenretinide对骨髓瘤细胞生物学特性的影响与其机制研究》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、第二军医大学硕士学位论文1．TheefficacyofnuclearreceptorinhibitorImportazoleonthebiologicalcharacteristicsofmultiplemyelomacells．1．1．ThenuclearreceptorimportinDisoverexpressedinCD138+MMprimercells．1．2．InterferenceimportinDcouldinhibitNF-r,BimporttonucleusandinduceapoptosisiIlNCI．H929cells．1．3．IPZi

2、nducesadose-andtime—dependentinhibitionofmyelomacellsgrowth．Aftertreatedwith8rtMIPZfor24h,thepercentageofSphasecellswasdecreasedfrom(53．55-4-0．94)％，(52．42-q：1．16)％to(45．19-士1．62)％，(42．27+1．02)％．Treatmentwith8州IPZ24hcouldinhibitNF-zBimporttonucleusandreduceitsDNAbindingactivity．Incont

3、rasttonormalbonemarrowmononuclearcells，treatmentof8州IPZfor2hcouldinhibitNF-1(Bimporttonucleusand12hcouldinducesignificantapoptosisinmyelomaprimercells．2．TheefficacyofretinoicacidderivativeFenretinideonthebiologicalcharacteristicsofmultiplemyelomasidepopulationcells．2．1．Fenretinideind

4、ucesadose-andtime—dependentinhibitionofmyelomacellsgrowth．2．2．FenretinidealoneorcombinationtherapycouldeffectivelyreducetheproportionofSPcellsinNCI-H929@<0．05)．2．3．SPcellsarearrestinG0／G1phase，andMPcellsaremainlyinSphaseandG2phase．2．4．ThecellularpotentialforclonogenicityofSPcellsisbe

5、tterthanMPcells．Fenretinidealoneorcombinationthempycouldeffectivelyreducethecolonyformingability，andbortezomibanddexamethasonehavelittleeffectonit．2．5．FenretinidecouldinduceSPcellapoptosisthroughproducereactiveoxygenspecies．IConclusion】1．ThenuclearreceptorinhibitorImportazoleinhibits

6、proliferationofmultiplemyelomacellsandinducesapoptosisbyblockingp65importtonucleus，whichcouldinhibittheactivatedNF-r,Bsignalpathway．2．MyelomasidepopulationcellsresistanttoMMclinicalfirst-linether印ybortezomibanddexamethasone．FeIlrefimdecouldtargetthesidepopulationcellsbyproducereactiv

7、eoxygenspecies．Bortezomibanddexamethasonecombination、析mfenretinidecouldplayasignificantanti—myelomaeffect．IKEYWORDS】Importazole，Fenretinide，myeloma,SPcells，NF-lcB，cellapoptosis-4-Importazole和Fertretinide对骨髓瘤细胞生物学特性的影响及其机制研究英文缩写RpmPBSBSAIFFBSDMS0FACSMTTEMSAPIPMSFpHHMinSld)KgGMgMlMmolN

8、molmM州nMCmMm