抑制JNK信号通路下调A549中LRP表达可增强顺铂化疗敏感性.pdf

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1、15l8中国肿瘤临床2013年第40卷第24期ChinJClinOncol2013，Vo1．40，No．24WWW．cjco．cn基础研究·抑制JNK信号通路下调A549中LRP表达可增强顺铂化疗敏感性：l：傅应亚韩晓黎黎友伦摘要目的：探讨在顺铂作用下的A549细胞中JNK信号通路与肺耐药蛋白LRP之间的相互关系。方法：用SP600125抑制JNK信号通路的活化，CCK一8法检测顺铂药物敏感性，流式细胞术检测细胞凋亡率，用Westernblotting法检测LRP、JNK、P—JNK的表达。结果：顺铂可活化JNK信号通路，上调LRP的表达；用SP600125抑制JN

2、K信号通路后，LRP的表达下调，增强了顺铂化疗敏感性，促进了细胞凋亡。结论：在A549细胞中，活化的JNK信号通路上调LRP的表达促进化疗耐药，因此阻断JNK信号通路为肺癌提供新的治疗靶点。关键词JNKLRPSP600125顺铂doi：10．3969／j．issn．1000—8179．20131036InhibitionoftheJNKpathwaydownregulateslung--resistancepro--teinandenhancesthechemosensitivityofA549cellstocisplatinYingyaFU，XiaoliHAN，Y

3、oulunLICorrespondenceto：YoulunLI；E—mail：liyoulun83@163．comDepartmentofRespiratoryMedicine，FirstAfiliatedHospitalofChongqingMedicalUniversity,Chongqing，ChinaThisworkwassupportedbytheStateKeyClinicalSpecialtyConstructionProject(No．WeiBanYiZhengHan[2012]No．649)AbstractObjective：Toinvestig

4、atetherelationshipbetweenthec-JunN—terminalkinase(JNK)pathwayandlung-resistanceprotein(LRP)．Methods：A549cellsweretreatedwithvariousconcentrationsofCDDPfor72h．TheLRPmRNAexpressionwasthenanalyzedusingreversetranscriptionPCR(RT-PCR)．LRP,JNK，andP-JNKwereanalyzedbyWesternblotting．TheA549cel

5、lswerethenpretreatedwithSP600125(2gg／mlto4~tg／m1)for1h．Afterward，CDDP(16gg／m1)wasaddedintotheculturefor72h．ACellCountingKit一8wasusedtoinvestigatethesensitivityofCDDPtotheA549cells．Flowcytometrywasusedtodetecttheapoptosisrate．TheLRPmRNAexpressionwasanalyzedusingRT-PCR．LRP,JNK，andP—JNKwe

6、reanalyzedbyWesternblotting．Results：CDDPin—ducedthemRNAandproteinexpressionofbothLRPandP-JNKinadose·-dependentmanner．PretreatmentwithSP600125enhancedthesensitivityofCDDPtotheA549cellsandincreasedtheapoptosisrate．However,theLRPmRNAandLRPexpressioninthepre—treatedcellswaslowerthanthatint

7、hepresenceofCDDPalone．Conclusion：InA549cells，CDDPinducestheLRPexpressionviatheJNKpathway．ThisresultsuggeststhatlungcancertherapyCanbeimprovedbytheadditionofCDDPtoinhibittheJNKsignalingpath—way．Keywords：c-JunN—terminalkinase(JNK)pathway,lung—resistanceprotein(LRP)，SP600125，CDDP肺癌是绝大多数