MIF抑制剂4-IPP通过调控NF-κB_CDK9_c-Myb轴抑制骨肉瘤的发生发展.pdfVIP

体内中通过蛋白印迹试验和免疫组化染色检测了4-IPP对骨肉瘤形成的影响。

结果：

体外实验表明，4-IPP通过抑制PI3K/AKT/NF-κB通路显著抑制骨肉瘤细胞的

增殖和转移。此外，4-IPP可通过下调MIF下游NF-κB/CDK9复合物介导的c-Myb

转录，从而抑制骨肉瘤的生长。在体内实验中，我们发现4-IPP通过抑制N-钙粘

蛋白，波形蛋白，MMP2，MMP9，Bcl-2，p-p65，CDK9和MIF的表达，并且促

进E-钙粘蛋白和Bax的表达而显著降低了裸鼠异种移植骨肉瘤的肿瘤发生。

结论：

我们的实验结果表明，4-IPP通过下调NF-κB/CDK9复合物介导的c-Myb转

录，从而抑制骨肉瘤的增殖和转移，并诱导细胞凋亡。因此，4-IPP可能是骨肉瘤

的一种新型治疗策略。

关键词：4-IPP；MIF：CDK9；c-Myb；骨肉瘤

MIFinhibitor4-IPPinhibitsthedevelopment

ofosteosarcomabyregulatingthe

NF-κB/CDK9/c-Mybaxis

ZhejiangUniversitySchoolofMedicineOrthopedics

MasterCandidateGaoJiawei

SupervisorProf.FanShunwu/HeDengwei

Abstract

Objective:

Osteosarcoma(OS)isacommonbonetumorcausedbymesenchymalcells.Among

allchildrenandadolescents,osteosarcomahasthehighestmortalityrate.Evenwitha

varietyoftreatmentmethodsincludingchemotherapy,the5-yearsurvivalrateisstillless

than70%duetotumorrecurrenceassociatedwithmetastasisanddrugresistance.In

addition,aneffectivetherapeutictargetordiagnosticmarkerforOShasnotyetbeen

determined,soitisdifficulttoimprovethetherapeuticeffect.Macrophagemigration

inhibitoryfactor(MIF)isapleiotropiccytokine.Asaninflammatoryfactorand

oncogenickinesin,MIFplaysavitalroleinthemicroenvironmentofosteosarcoma.

Although4-iodo-6-phenylpyrimidine(4-IPP)caninactivatethebiologicalfunctionsof

MIF,thereisnoresearchtoexplorethemolecularmechanismofosteosarcomaandits

anti-cancereffect.InordertoimprovetheprognosisofOS,betterstrategiesandnew

treatmentmethodsareurgentlyneededtodealwithdrugresistance.

Methods: