Anticancer Effects of 15d-Prostaglandin-J2 in Wild-Type and Doxorubicin-Resistant Ovarian Cancer Cells Novel Actions on SIRT1 and HDAC 英文参考文献.docVIP

下载本文档

2
0
约4.28万字
约 10页
2017-05-11 发布于上海
举报
版权申诉

Anticancer Effects of 15d-Prostaglandin-J2 in Wild-Type and Doxorubicin-Resistant Ovarian Cancer Cells Novel Actions on SIRT1 and HDAC 英文参考文献.doc

1、本文档共10页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Anticancer Effects of 15d-Prostaglandin-J2 in Wild-Type and Doxorubicin-Resistant Ovarian Cancer Cells Novel Actions on SIRT1 and HDAC 英文参考文献

AnticancerEffectsof15d-Prostaglandin-J2inWild-Type andDoxorubicin-ResistantOvarianCancerCells:Novel ActionsonSIRT1andHDAC EdwindeJong1.,PeterWinkel1.,KlaasPoelstra1,2,JaiPrakash 1,2 ¤ * 1DepartmentofPharmacokinetics,ToxicologyandTargeting,GroningenResearchInstituteforPharmacy,UniversityofGroningen,Groningen,TheNetherlands,2BiOrion TechnologiesBV,MediTechCenterUMCG,L.J.Zielstraweg1,Groningen,TheNetherlands Abstract 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2), an arachidonic metabolite and a natural PPARc agonist, is known to induceapoptosisintumorcells.Inthisstudy,weinvestigatednewtherapeuticpotentialsof15d-PGJ2bydeterminingits anticancer effects in wild-type and doxorubicin-resistant ovarian carcinoma cells. Despite high expression of resistance- inducinggeneslikeMDR1,Bcl2andBcl-xl,15d-PGJ2stronglyinducedapoptosisindoxorubicin-resistant(A2780/AD)cells similartothewild-type(A2780).Thiswasfoundtoberelatedtocaspase-3/7-andNF-kBpathwaysbutnottoitsPPARc agonisticactivity.15d-PGJ2alsowasabletoreducethedoxorubicinresistanceofA2780/ADcellsatlowdosesasconfirmed bytheinhibitionofgeneexpressionofMDR1(p-glycoprotein)andSIRT1(adrugsenescencegene).Wealsoinvestigated effects of 15d-PGJ2 on cell migration and transformation using a wound-healing assay and morphological analyses, respectively.Wefoundthat15d-PGJ2inhibitedmigrationmostlikelyduetoNF-kBinhibitionandinducedtransformationof theround-shapeA2780/ADcellsintoelongatedepithelialcellsduetoHDAC1inhibition.Usinga15d-PGJ2analog,wefound themechanismofactionofthesenewactivitiesof15d-PGJ2onSIRT1andHDAC1geneexpressionsandenzymeactivities. Inconclusion,thepresentstudydemonstratesthat15d-PGJ2hasahightherapeuticpotentialtokilldrug-resistanttumor cells and, the newly described inhibitory effects of this cyclo-oxygenase product on SIRT1 and HDAC will provide new opportunitiesforcancertherapeutics. Citation:deJongE,WinkelP,PoelstraK,PrakashJ(2011)AnticancerEffectsof15d-Prostaglandin-J2inWild-TypeandDoxorubicin-ResistantOvarianCancerC