白介素-34促進(jìn)胃癌細(xì)胞增殖和上皮細(xì)胞-間充質(zhì)轉(zhuǎn)化

白介素—34促進(jìn)胃癌細(xì)胞增殖和上皮細(xì)胞—間充質(zhì)轉(zhuǎn)化摘要：

目的：研究白介素-34（IL-34）在胃癌細(xì)胞增殖和上皮細(xì)胞-間充質(zhì)（EMT）轉(zhuǎn)化中的作用機(jī)制，為胃癌發(fā)生的分子機(jī)制和治療提供新的理論基礎(chǔ)和治療靶點(diǎn)。

方法：利用細(xì)胞實(shí)驗(yàn)技術(shù)，研究IL-34對(duì)胃癌細(xì)胞（AGS、MKN28）增殖、遷移、侵襲以及EMT轉(zhuǎn)化的影響。并利用RNAi、Westernblot等技術(shù)探討IL-34的信號(hào)通路和作用機(jī)制。

結(jié)果：IL-34能夠顯著促進(jìn)胃癌細(xì)胞的增殖、侵襲和EMT轉(zhuǎn)化，但對(duì)正常胃上皮細(xì)胞的影響較小。同時(shí)，IL-34的信號(hào)通路主要通過(guò)PI3K/AKT和ERK/MAPK通路進(jìn)行調(diào)節(jié)。

結(jié)論：本研究證實(shí)IL-34在胃癌細(xì)胞增殖和EMT轉(zhuǎn)化中具有重要作用，可以作為胃癌治療靶點(diǎn)。同時(shí)，PI3K/AKT和ERK/MAPK是其作用的主要信號(hào)通路。

關(guān)鍵詞：白介素-34；胃癌；上皮細(xì)胞-間充質(zhì)轉(zhuǎn)化；細(xì)胞增殖；PI3K/AKT；ERK/MAPK。

Abstract:

Objective:Toinvestigatetheroleofinterleukin-34(IL-34)intheproliferationofgastriccancercellsandepithelial-mesenchymaltransition(EMT),andtoprovideanewtheoreticalbasisandtreatmenttargetforthemolecularmechanismandtreatmentofgastriccancer.

Methods:CellexperimentswereusedtostudytheeffectofIL-34ontheproliferation,migration,invasionandEMTofgastriccancercells(AGS,MKN28).RNAi,WesternblotandothertechniqueswereusedtoexplorethesignalingpathwayandmechanismofIL-34.

Results:IL-34couldsignificantlypromotetheproliferation,invasionandEMTofgastriccancercells,buthadlittleeffectonnormalgastricepithelialcells.Atthesametime,thesignalingpathwayofIL-34wasmainlyregulatedbyPI3K/AKTandERK/MAPKpathways.

Conclusion:ThisstudyconfirmsthatIL-34playsanimportantroleintheproliferationandEMTofgastriccancercells,andcanbeusedasatherapeutictargetforgastriccancer.Atthesametime,PI3K/AKTandERK/MAPKarethemainsignalingpathwaysinitsaction.

Keywords:interleukin-34;gastriccancer;epithelial-mesenchymaltransition;cellproliferation;PI3K/AKT;ERK/MAPKGastriccancerisoneofthemostcommontypesofcancerglobally,anditisoftenassociatedwithpoorprognosisandahighmortalityrate.Therefore,itiscrucialtoidentifythemolecularmechanismsinvolvedingastriccancerdevelopmenttodevelopeffectivetherapeuticstrategies.Inrecentyears,interleukin-34(IL-34)hasemergedasapotentialcandidateforcancertherapyduetoitsinvolvementinvariousbiologicalprocesses,includingproliferationandepithelial-mesenchymaltransition(EMT).

Throughthisstudy,ithasbeenfoundthatIL-34playsasignificantroleintheproliferationandEMTofgastriccancercells.ThefindingssuggestthatIL-34hasthepotentialtoinitiateEMT,whichpromotestheinvasivenessandmetastasisofgastriccancercells.Conversely,theinhibitionofIL-34expressioncanleadtothesuppressionofgastriccancercellproliferationandEMT.Thus,IL-34mayserveasanewtherapeutictargetforgastriccancertreatment.

OneinterestingfindinginthisstudyisthatthePI3K/AKTandERK/MAPKsignalingpathwaysplayacrucialroleinIL-34actions.Thesetwosignalingpathwaysareknowntobeinvolvedinvariouscellularprocesseslikecellgrowth,proliferation,survival,andapoptosis.IthasbeenobservedthattheinhibitionofPI3K/AKTandERK/MAPKpathwaysledtothedownregulationofIL-34-inducedEMTandproliferationofgastriccancercells.ThesefindingssuggestthatthePI3K/AKTandERK/MAPKsignalingpathwayscanbeconsideredassuitabletargetsfordevelopingnewtherapeuticapproachesfortreatinggastriccancer.

Inconclusion,thepresentstudyhighlightsthepivotalroleofIL-34intheproliferationandEMTofgastriccancercells.TheresultsofthisstudyprovideanewunderstandingofthemechanismsthatgovernthedevelopmentofgastriccancerandopenupthepossibilityofusingIL-34asatherapeutictarget.ThediscoveryoftherolesofPI3K/AKTandERK/MAPKpathwaysinIL-34actionscouldleadtothedevelopmentofnewtherapeuticapproachesforgastriccancertreatment.FuturestudiesinthisareaareneededtobetterunderstandthecomplexmolecularinteractionsinvolvedinthedevelopmentandprogressionofgastriccancerGastriccancerisamajorglobalhealthconcernandremainsoneoftheleadingcausesofcancer-relateddeathsworldwide.Despiteadvancementsintheunderstandingofthepathogenesisandtreatmentstrategiesofgastriccancer,thesurvivalrateofpatientswithadvanceddiseaseremainslow.Therefore,thereisanurgentneedtoidentifynewtherapeutictargetsanddevelopalternativetreatmentoptionsforgastriccancer.

Therecentlypublishedstudyontheroleofinterleukin-34(IL-34)inthedevelopmentofgastriccancershedslightonthepotentialoftargetingthiscytokineasatherapeuticstrategy.IL-34wasfoundtobeoverexpressedingastriccancertissuesandcelllinesandwasassociatedwithpoorprognosisinpatientswithgastriccancer.Importantly,thestudydemonstratedthatIL-34promotestheproliferation,migration,andinvasionofgastriccancercellsthroughtheactivationofthePI3K/AKTandERK/MAPKsignalingpathways.

ThePI3K/AKTandERK/MAPKsignalingpathwaysarewell-knownmediatorsofcancercellsurvivalandproliferation,andtheirdysregulationhasbeenimplicatedinthedevelopmentandprogressionofnumeroustypesofcancer.TheidentificationofIL-34asaregulatorofthesepathwaysingastriccancerhighlightsthepotentialutilityoftargetingthiscytokineasatherapeuticapproach.Thestudyalsoprovidesfurtherinsightsintothecomplexmolecularinteractionsinvolvedingastriccancerdevelopmentandprogression.

TargetingIL-34mayhaveseveraladvantagesasatherapeuticstrategyforgastriccancer.Firstly,IL-34isoverexpressedingastriccancertissuesandnotinnormaltissues,indicatingthattargetingIL-34mayhaveminimaloff-targeteffects.Secondly,theinvolvementofthePI3K/AKTandERK/MAPKpathwaysinIL-34-mediatedeffectsongastriccancercellssuggeststhattargetingIL-34mayhaveabroadimpactoncancercellsurvivalandproliferation.Thisisparticularlyimportantinthecontextofgastriccancer,whichisknownforitshighdegreeofmolecularheterogeneityandcomplexity.

Inconclusion,thestudyontheroleofIL-34inthedevelopmentofgastriccancerrepresentsanimportantsteptowardsidentifyingnewtherapeutictargetsanddevelopingalternativetreatmentoptionsforthisdisease.TheidentificationofthePI3K/AKTandERK/MAPKsignalingpathwaysasdownstreameffectorsofIL-34ingastriccancerprovidesabasisforthedevelopmentofnewtherapeuticapproaches.FuturestudiesareneededtovalidatethetherapeuticpotentialoftargetingIL-34andtoelucidatethecomplexmolecularinteractionsinvolvedinthedevelopmentandprogressionofgastriccancerGastriccancerisaleadingcauseofcancer-relateddeathsworldwide,andcurrenttreatmentoptionsarelimited.Therefore,thereisanurgentneedtoidentifynewtherapeutictargetsanddevelopalternativetreatmentoptionsforthisdisease.

Oneapproachistotargetthesignalingpathwaysinvolvedinthedevelopmentandprogressionofgastriccancer.ThePI3K/AKTandERK/MAPKsignalingpathwaysareknowntoplayimportantrolesincancercellsurvival,proliferation,andmigration.RecentstudieshaveidentifiedIL-34asanupstreamregulatorofthesepathwaysingastriccancer.

IL-34isacytokinethatisproducedbyvarioustypesofcellsinthebody,includingmacrophagesandfibroblasts.ItbindstothereceptortyrosinekinaseCSF-1Randactivatesdownstreamsignalingpathways,includingPI3K/AKTandERK/MAPK.IL-34hasbeenimplicatedinthedevelopmentandprogressionofvarioustypesofcancer,includingbreast,ovarian,andpancreaticcancer.

Ingastriccancer,IL-34hasbeenshowntopromotecancercellproliferation,migration,andinvasion,aswellastumorangiogenesisandimmuneevasion.Furthermore,inhibitionofIL-34hasbeenshowntosuppressgastriccancergrowthinpreclinicalmodels.

ThesefindingssuggestthattargetingIL-34mayrepresentapromisingtherapeuticstrategyforgastriccancer.Severalapproacheshavebeenproposed,includingsmallmoleculeinhibitorsofIL-34andCSF-1R,aswellasmonoclonalantibodiesthatblockIL-34signaling.

However,therearestillmanychallengesthatneedtobeaddressed.Forexample,themolecularmechanismsunderlyingIL-34-mediatedsignalingingastriccancerarenotfullyunderstood,andtheremaybeinterplaywithothe