3655.2,3吲哚醌抑制人神經(jīng)母細胞瘤侵襲和轉(zhuǎn)移的fak信號通路研究

1、分類號：R739.4密級：不保密UDC：610學校代碼：11065碩士學位論文2，3吲哚醌抑制人神經(jīng)母細胞瘤侵襲和轉(zhuǎn)移的吲哚醌抑制人神經(jīng)母細胞瘤侵襲和轉(zhuǎn)移的FAKFAK信號通路研究信號通路研究陳志祥指導教師侯琳教授學科專業(yè)名稱生物化學與分子生學物學論文答辯日期2016年5月26日AbstractObjective:Previousresearchhasshownthatisatinhasaninhibityeffectfavariety

2、oftums.Isatinisabletoaltertheproliferationofhumanneuroblastomacells(SHSY5Y)byblockingcellcycle.TheaimofthepresentstudywastoinvestigateinvasionmigrationofSHSY5Ycellstherelatedmolecularmechanism.Methods:SHSY5Ycellsweretrea

3、tedwithisatinatvariousconcentrations(25μmolL50μmolL100μmolL200μmolL).ThemigrationabilityofSHSY5Ycellswereassessedthroughtranswellmigrationassays.MMP9mRNAwereanalyzedviaRTPCR.Theproteinsthatrelatedwereanalyzedviawesternbl

4、otting.FAKinhibitPF562271wereusedinpositivecontrolgroup.Results:AftertreatedwithisatinthemigrationofSHSY5Ycellsdecreased.RTPCRwesternblottingshowedthattheexpressionofMMP9decreasedthereisadeclineinthephosphylationlevelofF

5、AK(Tyr397)ERK(Thr202Tyr204)Paxillin(Tyr118)bothinisatintreatedgrouppositivecontrolgroup.ThephosphylationlevelofSAPKJNK(Thr183Tyr185)differenceswereofnosignificancebetweenisatintreatedgroupcontrolgroupwhilethephosphylatio

6、nlevelofSAPKJNK(Thr183Tyr185)inpositivecontrolgroupweresignificantlylowercomparedwithcontrolgroup.Conclusions:IsatincaninhibitmigrationinvasionofSHSY5YcellsFAKsignalpathwaymaybeinvolvedintheprocess.ThephosphylationofFAKw

7、asaffectedbyisatincausingchangesofrelatedproteinswhichleadtodecreaseintheexpressionofMMP9.InthiswaytheinvasionofSHSY5Ycellswasaffected.ThephosphylationofFAKpaxillinwasaffectedcausingnegativeinfluenceinthereganizationofcy

8、toskeletonwhichisimptantfmetastasis.BesidesCellmotilitywasdecreasedwhenphosphylationofpaxillinwasaffected.Postgraduatestudent:ZhixiangChen(BiochemistryMolecularBiology)DirectedbyProf.HouLinKeywds:IsatinNeuroblastomaInvas