塞来昔布对肝癌HepG2 HepG3细胞的免疫增敏作用.pdf

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1、-1336·安徽医药AnhuiMedicalandPharmaceuticalJournal2014Jul；18(7)◇药物临床◇塞来昔布对肝癌HepG2HepG3细胞的免疫增敏作用刘永庆，童斯浩，鲍扬漪，王成宏(安徽医科大学第三附属医院1．肝胆外科；2．肿瘤科，安徽合肥230061)摘要：目的探讨选择性环氧合酶一2(COX-2)抑制剂塞来昔布(Celecoxib)对人肝癌HepG2和HepG3细胞株对肿瘤坏死因子相关的凋亡诱导配体(TRAIL)的增敏作用及其可能机制。方法以人HepG2HepG3肝癌细胞为研究对象，以塞来昔布和TRAIL作为干预手段

2、，采用四甲基偶氮唑蓝(M1TI1)法检测塞来昔布对肝癌细胞株的增殖抑制作用，采用流式细胞术，检测塞来昔布联合TRAIL对HepG2，HepG3细胞的凋亡及DR4，DR5的表达。塞来昔布与不同效靶比的细胞因子诱导的杀伤细胞(CIK)联合作用于人肝癌细胞株，经LDH检测法检测其杀伤作用。结果塞来昔布及TRAIL对人肝癌HepG2和HepG3细胞株均有显著抑制作用，塞来昔布联合TRAIL可显著增敏TRAIL对HepG2和HepG3的杀伤，其差异具有统计学意义(P<0．05)，经过塞来昔布预处理的肝癌细胞更易被CIK细胞杀伤。结论塞来昔布对人肝癌HepG2和

3、HepG3细胞株具有明显细胞毒性，联合TRAIL及CIK可显著增敏后者对肝癌细胞的杀伤效应，其机制可能与塞来昔布上调DR4，DR5有关。关键词：原发性肝癌；塞来昔布；COX．2抑制剂；TRAIL；CIKdoi：10．3969／j．issn．1009—6469．2014．07．050CelecoxibsensitizesHepatomacellstoimmune·mediatedcytotoxicityLIUYong—qing，TONGSi—hao，BAOYang．yi，etal(1．DepartmentofHepatobiliarySurgery；2

4、．DepartmentofOncology，ThirdAffiliatedHospitalofAnhuiMedicalUniversity，Hefei，Anhui230061，China)Abstract：ObjectiveToinvestigatetheeffectofCOX-2inhibitorcelecoxibonthegrowthofhepaticcarcinomaHepG2andHepG3andexploreitsmechanism．MethodsInhumanhepaticcarcinomacelllineHepG2，HepG3asthe

5、researchobject，usingcelecoxibandTRAILasameansofintervention，thefunctionofcelecoxiboncellproliferationinhibitionwasobservedindifferentconcentrationandtimebyMTF，byusingflowcytometrictechniquefortheobservationofcelecoxibcombinedwithTRAILonhepatomacellapoptosisandexpresschangeofDR4

6、andDR5．TheapoptosiseffectofCelecoxibcombinedwithdifferentconcentrationsCIKcellsonhepatomacellswasdetectedbyLDHassay．ResultsCelecoxibandTRAILhasobviousinhibitioneffectonhepaticcarcinomacelllineHepG2andHepG3．CelecoxibwouldsignificantlysensitizeTRAILtoHepG2andHepG3，ithasstatistica

7、lsignificance(P<0．05)．Celecoxibpre—treatmentmadehepatomacellsmoresusceptibletoCIKcellkilling．ConclusionCelecoxibhasobviouslycytotoxiconhepaticcarcino—macelllineHepG2，HepG3．CelecoxibcombinewithTRAILandCIKwouldsignificantlysensitizeitscytotoxiceffect．Themechanismmaybeassociatedwi

8、thincreasedexpressionofDR4／5bycelecoxibpretreatment．Ke