Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR 英文参考文献.docVIP

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Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR 英文参考文献.doc

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Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR 英文参考文献

CamboginIsPreferentiallyCytotoxictoCellsExpressing PDGFR ZeTian1,4*,JieShen1,FengfeiWang2,PeigenXiao1,JunshanYang1,HetianLei1,3,AndriusKazlauskas3, IsaacS.Kohane4,ErxiWu2* 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, United States of America, 3Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, United States of America, 4Informatics Program, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, UnitedStatesofAmerica Abstract Platelet-derivedgrowthfactorreceptors(PDGFRs)havebeenimplicatedinawidearrayofhumanmalignancies,including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeuticshasbeenachievedduringthepastdecades,MBremainsahorriblechallengetothephysiciansandresearchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogintriggerssignificantSphasecellcyclearrestandapoptosisviadownregulationofcyclinAandE,andactivationof caspases.Moreimportantly,furthermechanisticstudiesdemonstratedthatcambogininhibitsPDGFRsignalinginDaoyand geneticallydefinedmouseembryofibroblast(MEF)celllines.Theseresultssuggestthatcamboginispreferentiallycytotoxic tocellsexpressingPDGFR.OurfindingsmayprovideanovelapproachbytargetingPDGFRsignalingagainstMB. Citation:TianZ,ShenJ,WangF,XiaoP,YangJ,etal.(2011)CamboginIsPreferentiallyCytotoxictoCellsExpressingPDGFR.PLoSONE6(6):e21370.doi:10.1371/ journal.pone.0021370 Editor:MikhailV.Blagosklonny,RoswellParkCancerInstitute,UnitedStatesofAmerica ReceivedMarch26,2011;AcceptedMay25,2011;PublishedJune21,2011 Copyright:?2011Tianetal.Thisisanopen-accessart