乙酰胆碱酯酶在肝癌中的功能及其分子作用机制的分析

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1、乙酞胆碱酷酶在肝癌中的功能及其分子作用机制的研究英文摘要TheStudyontheFunctionandtheMolecularMechanismofAeetyleholinesteraseinHePaticCareinogenesis[AbstraetlInrecentyears，cancerhasbeenhowntobeasystemicdiseasewithalargevarietyofdeviationsofoneogenesandtumor-suPPressorgenes.Livercane

2、er，ineludinghePatocellularcarcinoma(HCC)andhePatoblastoma，15oneofthemostPrevalentandlethaleaneersinChina，RecentstudiesrevealedthatthePathogenesisanddeveloPmentofHCC15involvedinalargevarietyofdysregulationsofsignalingPathwaysanddeviationsofoneogenesand/o

3、rtumorsuPPressorgenes.ourPreviousstudyofalarge一scaleeomPlementaryDNAtransfeetionsereeningshowedthatsomeeytokinesorreeePtorsdrivenfromneuralsystemarerelatedtotheProliferationofhePatoeellulareareinomaeells.hithePresentstudy，weinvestigatedtheexisteneeand九n

4、ctionoftheeholinergiesysteminhePatieeancereellsandidentifiedthedown一regulationofitskeycomPonentaeetyleholinesterase(ACHE)，andfortherexPloreditsfunetionandthemolecularmeehanismofACHEinhePatieeancereells.ACHEPlaysimPortantrolesintheeholinergiesystem，andit

5、sdysregulationinvolvesinavarietyofhumandiseases.Howeve瓦therolesandimPlicationsofACHEinhePatieeaneerremainelusive.Here，wedemonstratedthattheeholinergiesystemexistsinhePaticeaneereells.ImPortantl又ACHE15significantlydown一regulatedinHCCtissues.Boththereeomb

6、inantACHEProteinandtheover-exPressionofACHEbylenti一virusobviouslyinhibittheeellProliferationrate，thecolonyformationabilityinvitroaswellastumorformationcapabilityinvl’vo.Furtherstu即showedthatAehenhancesHCCeellProliferationandACHEsuPPressescellProliferati

7、onviaitsenzynlatieaetivityofcatalyzinganddegradingacetyleholine(Aeh).Moreover，ACHEeouldinaetivatemitogen一activatedProteinkinase(MAPK)andPI3K/A火tPathwaysinHCCeells;anditcouldobviouslyinereasetheaetivationofglyeogens邓thasekinase3p(GSK3p)，thusresultinginp一

8、eatenindegradationandeyelinDlsuPPression.Inaddition，thereeombinantACHEProteinortheinereaseofACHEexPressioneouldremarkablyenhancedthedrug一indueedaPoPtosisinhePaticcaneercellsandsensitizethesecellstochemotherapeuticaldrugs，i.e.Adri