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1、上海交通大学硕士学位论文AG490联合吉西他滨对人胰腺癌细胞生长的体外研究姓名：陈钢申请学位级别：硕士专业：外科学指导教师：裘正军20070510上海交通大学硕士研究生学位论文西他滨组(P<0.05)；而先用吉西他滨再用AG490组细胞增殖率明显低于先用AG490再用吉西他滨组(P<0.05)，先用吉西他滨再用AG490组细胞凋亡率明显高于于先用AG490再用吉西他滨组(P<0.05)。结论:吉西他滨，AG490或两者联合均可抑制人胰腺癌细胞增殖，促进细胞凋亡。AG490通过阻断JAK激活，抑制S
2、TAT3活化，而下调CyclinD1，Bcl-xl，Survivin的表达，上调Bax的表达而抑制人胰腺癌细胞的增殖，促进细胞的凋亡；吉西他滨AG490联合可以起到协同作用；先用吉西他滨后用AG490的作用优于先用AG490后用吉西他滨。关键词:胰腺肿瘤；信号转导与转录激活因子3；增殖；凋亡-V-上海交通大学硕士研究生学位论文THEEFFECTOFAG490COMBINEDWITHGEMCITABINEONTHEGROWTHOFHUMANPANCREATICCANCERCELLSINVITROAB
3、STRACTObjective:ToinvestigatetheeffectsandmechanismofAG490,Gemcitabine,theircombinationanddifferentdrugscheduleontheproliferationandapoptosis,theexpressionsoftheSTAT3,p-STAT3,CyclinD1,Bcl-xl,Bax,andSurvivinwasdetectedunderdifferenttreatmentsinhumanpan
4、creaticcancercelllinesinvitro.Methods:Theexperimentwasdividedintosixgroupsaccordingtodifferentdrugtreatment:thecontrolgroup,theAG490group,theGemcitabinegroup,theAG490+Gemcitabinegroup,theAG490followedbyGemcitabinegroupandtheGemcitabinefollowedbyAG490g
5、roup.ThecellproliferationwasevaluatedbyMTTassay.Theflowcytometrywasusedtoobservethecellapoptosis.ThetranscriptionalandtranslationalexpressionsofSTAT3,CyclinD1,-VI-上海交通大学硕士研究生学位论文Bcl-xl,BaxandSurvivinwereexaminedbyWesternblotandRT-PCR.Results:Thecellgr
6、owthratesoftheAG490groupandtheGemcitabinegroupwere(2.20±0.25)and(2.30±0.22)respectively,thatweresignificantlylowerthanthatofthecontrolgroup(3.78±0.42).TheapoptosisproportionoftheAG490groupandtheGemcitabinegroupwere(35.40±3.08)%and(34.64±1.38)%respecti
7、vely,thatweresignificantlyhigherthanthatofthecontrolgroup(16.49±1.45)%.Theexpressionofp-STAT3proteinoftheAG490groupwassignificantlylessthanthatofthecontrolgroup(P<0.05).TheexpressionofmRNAsandproteinsofCyclinD1,Bcl-xl,andSurvivinwerelessthanthatofthec
8、ontrolgroupsignificantlyaswell.ButtheexpressionofmRNAandproteinofBaxweresignificantlyhigherthanthatofthecontrolgroup.TheresultsoftheGemcitabinegroupweresimilartothatofthecontrolgroup.ThecellgrowthrateoftheAG490combinedwithGemcitabinegroupwassi
