α干扰素增强骨肉瘤细胞对依托泊苷敏感性实验探究

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1、α干扰素增强骨肉瘤细胞对依托泊苷敏感性实验探究　　α干扰素增强骨肉瘤细胞对依托泊苷敏感性的实验研究黄秀芳1原向伟21.广东省江门市中心医院病理科，广东江门529030；2.广东省江门市中心医院骨科，广东江门529030[摘要]目的探讨α干扰素（IFN-α）在人骨肉瘤U2OS和MG63细胞中对依托泊苷敏感性的作用及其机制。方法采用IFN-α和依托泊苷单独或联合处理骨肉瘤U2OS和MG63细胞72h，应用流式细胞术和DNALadder检测细胞凋亡的变化，Westernblot法检测PARP、p53、MDM2、Bax、Bcl-2的表达。结果流式

2、细胞术表明IFN-α在p53正常的U2O啊、胞中明显增强依托泊苷诱导的凋亡（P0.05）；DNALadder表明与单药组相比，IFN-α与依托泊苷联用72h在U2OS细胞出现明显的DNA梯形条带，而在MG63细胞中无此现象；Westernblot结果表明在U2OS细胞中联合用药组出现PARP的明显裂解活化，并且IFN-α明显增强依托泊苷引起的p53信号通路p53、MDM2、Bax等凋亡基因的表达，并抑制抗凋亡基因Bcl-2的表达，而在MG63细胞中则无此现象。结论13IFN-α能够通过激活p53依赖性信号通路增强依托泊苷诱导的骨肉瘤U2O

3、S细胞凋亡，联合应用IFN-α和传统化疗药物如依托泊苷可能成为提高骨肉瘤化疗敏感性的有效途径。[关键词]α干扰素；依托泊苷；骨肉瘤；凋亡；p53[中图分类号]R738.1[文献标识码]A[文章编号]1673-7210（2014）03（a）-0004-05ExperimentalstudyofIFN-αforenhancingsensitivitytoEtoposideinhumanosteosarcomacellsHUANGXiufang1YUANXiangwei21.DepartmentofPathology，JiangmenCentr

4、alHospital，GuangdongProvince，Jiangmen529030，China；2.DepartmentofOrthopaedicSurgery，JiangmenCentralHospital，GuangdongProvince，Jiangmen529030，China[Abstract]ObjectiveTostudyeffectofIFN-αonthesensitivitytoEtoposideinhumanosteosarcomaU2OSandMG63cellswithitsmolecularmechanisms

5、.MethodsU2OSandMG63cellsweretreatedwithIFN-αandEtoposide，aloneorincombination，for72h.FlowcytometryanalysisandDNALadderwereusedtoexamineapoptosis.Westernblot13wasusedtodetermineexpressionofPARP，p53，Bax，Mdm2andBcl-2.ResultsIFN-αenhancedEtoposide-inducedapoptosisinp53-wildU2

6、OScells（P0.05）.IFN-α+EtoposidecombinationresultinobviousDNALadderinU2OS，butnotMG63cellsandactivationofPARPinU2OScells.Theenhancedapoptosiswasassociatedwiththeaccumulationoftranscriptionallyactivep53accompaniedwiththeincreasedBaxandMDM2，aswellasdecreasedBcl-2，inU2OScells，w

7、hichwasnotobservedinMG63cells.ConclusionIFN-αenhancesEtoposide-inducedapoptosisinhumanosteosarcomaU2OScellsbyactivationofp53-dependentsignalpathway.ThisworkimpliesthatrationalcombinationwithIFN-αandchemotherapyincludingEtoposidemaybeausefulstrategyforenhancingthechemosens

8、itivityofosteosarcoma.[Keywords]IFN-α；Etoposide；Osteosarcoma；Apoptosis；p5313骨肉瘤高发于青少年人群，居于人类骨骼系统