中山大學(xué)腫瘤防治中心_第1頁(yè)
中山大學(xué)腫瘤防治中心_第2頁(yè)
中山大學(xué)腫瘤防治中心_第3頁(yè)
中山大學(xué)腫瘤防治中心_第4頁(yè)
中山大學(xué)腫瘤防治中心_第5頁(yè)
已閱讀5頁(yè)，還剩13頁(yè)未讀， 繼續(xù)免費(fèi)閱讀

下載本文檔

版權(quán)說(shuō)明：本文檔由用戶提供并上傳，收益歸屬內(nèi)容提供方，若內(nèi)容存在侵權(quán)，請(qǐng)進(jìn)行舉報(bào)或認(rèn)領(lǐng)

文檔簡(jiǎn)介

EmodinazidemethylanthraquinonederivativeinducesproteasomaldegradationofHer2/neuinHer2/neu-overexpressingcancercells

Li-sheng

Zheng,Yan-yanYan,Li-wuFuCancerCenter,SunYat-senUniversity2010.5

1

OverexpressionofHER2/neu

iscommoninmultiplemalignancies,

includingbreast,ovarian,lungandprostatecancer,etc.

ClinicalstudieshavedemonstratedthatelevatedHER2/neu

expressioncorrelateswithpoorprognosisinmultiplemalignancies

Duringthelastdecade,HER2/neuhasbeentargetedinordertodevelopnovelanticancerdrugs

Trastuzumab(Herceptin?)

Lapatinib(Tykerb)

------efficacyandlong-termuseinpatientsarequitelimitedduetoresistancetotheseinhibitorsorseveresideeffectsBackground2

Anthraquinonederivative

ActiveingredientofvariousChineseherbsincludingrhubarb,

Polygonum

cuspidatum

Anti-bacterial,anti-inflammatory,anti-tumor

EmodinStructureofemodinBackground

Blockauto-ortrans-phosphorylationofHER2/neu

IncreasesthesusceptibilityofHER2/neu

overexpressingcancercellstostandardcytotoxictherapeuticagents3

anticanceractivitynotobvious

sideeffectssuchascardiactoxicity

WeandProfessorLian-quan

Gugroup(SchoolofChemistryandChemicalEngineering,SunYat-senUniversity)modifiedstructureofemodinandsynthesizedaseriesofemodinanthraquinonederivativesBackgroundStructureofemodinAMAD4AMADshowspotentanticancereffectonbreastcancerandlungadenocarcinomacelllines

5AMADinhibitsthegrowthofhumannon-smallcelllungcarcinomaH460cellxenograftsinnudemice

6AMADdown-regulatesHer2/neuproteinexpression

7AMADinhibitsHer2/neudownstreamsignalingpathways8AMADincresesHer2/neuproteininstability

9AMADinducespolyubiquitinationofHER2/neu

10AMADdepletesHER2/neubyproteasomaldegradation

11AMADinhibitedHer2/neubindingtoHsp9012KnockdownHer2/neubysiRNAinducesgrowthinhibition13CombinationofAMADandsiRNAagainstHer2synergisticallyinducesapoptosis

14CombinationofAMADandsiRNAagainstHer2furtherpromotesHER2/neudegradationandinhibitesdownstreamsignalingpathways15DiscussionApigenin

andGeldanamycincaninduceHER2proteindegradationbyubiquitin-proteasomepathway

DownregulationofHER2byAMADisdependentofHer2proteinstabilitybutnotmRNAlevel

DissociationofHer2/Hsp90heterocomplexbyAMADmaybecorrelatedwithpromotedproteasomaldegradationofHer2protein

HER2specific:AMADdoesnotdecreasetheexpressionofHer1protein16

AMADexertspotentcytotoxiceffectsonMDA-MB-453andCalu-3cells.

AMADinhibitstheproliferationviaMAPKandPI(3)K/Aktpathwaysignaling.

AMADtargetsHER2/neutoubiquitinylation-dependentproteasomaldegradation.

Combine

溫馨提示

  • 1. 本站所有資源如無(wú)特殊說(shuō)明，都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請(qǐng)下載最新的WinRAR軟件解壓。
  • 2. 本站的文檔不包含任何第三方提供的附件圖紙等，如果需要附件，請(qǐng)聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
  • 3. 本站RAR壓縮包中若帶圖紙，網(wǎng)頁(yè)內(nèi)容里面會(huì)有圖紙預(yù)覽，若沒(méi)有圖紙預(yù)覽就沒(méi)有圖紙。
  • 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
  • 5. 人人文庫(kù)網(wǎng)僅提供信息存儲(chǔ)空間，僅對(duì)用戶上傳內(nèi)容的表現(xiàn)方式做保護(hù)處理，對(duì)用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯，并不能對(duì)任何下載內(nèi)容負(fù)責(zé)。
  • 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容，請(qǐng)與我們聯(lián)系，我們立即糾正。
  • 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時(shí)也不承擔(dān)用戶因使用這些下載資源對(duì)自己和他人造成任何形式的傷害或損失。

最新文檔

評(píng)論

0/150

提交評(píng)論