冬凌草甲素阻滯人胃癌SGC-7901細(xì)胞于M期的機(jī)理研究

冬凌草甲素阻滯人胃癌SGC-7901細(xì)胞于M期的機(jī)理研究摘要：胃癌一直是全球公認(rèn)的難治性疾病，當(dāng)前尚無(wú)可避免的風(fēng)險(xiǎn)因素。因此，探尋胃癌治療的新方法和新靶點(diǎn)對(duì)胃癌的治療具有重要的意義。本研究旨在探究冬凌草甲素對(duì)人胃癌SGC-7901細(xì)胞周期的影響，以期為胃癌的治療提供新的思路。

本實(shí)驗(yàn)選用了胃癌SGC-7901細(xì)胞作為研究對(duì)象。通過(guò)細(xì)胞實(shí)驗(yàn)，我們發(fā)現(xiàn)冬凌草甲素能夠抑制SGC-7901細(xì)胞增殖并且能夠引起S期和M期細(xì)胞的積累，提示冬凌草甲素在SGC-7901細(xì)胞中的抗腫瘤作用可能與細(xì)胞周期的調(diào)節(jié)有關(guān)。進(jìn)一步的研究表明，冬凌草甲素可阻止SGC-7901細(xì)胞進(jìn)入細(xì)胞分裂的后期并誘導(dǎo)細(xì)胞凋亡，并通過(guò)激活絲裂原活化蛋白激酶(MAPKs)信號(hào)通路進(jìn)而抑制腫瘤細(xì)胞的增殖。

因此，我們得出結(jié)論：冬凌草甲素可以抑制人胃癌SGC-7901細(xì)胞的增殖，并且作用機(jī)制可能是通過(guò)調(diào)節(jié)細(xì)胞周期及激活MAPKs信號(hào)通路引起的。這項(xiàng)研究揭示出冬凌草甲素可作為治療胃癌的潛在藥物靶點(diǎn)，為胃癌的治療提供了新的思路和方法。

關(guān)鍵詞：胃癌，SGC-7901細(xì)胞，冬凌草甲素，細(xì)胞周期，MAPKs信號(hào)通路。

Abstract:Gastriccancerhasalwaysbeenrecognizedasadifficult-to-treatdiseaseglobally,andtherearecurrentlynoavoidableriskfactors.Therefore,exploringnewmethodsandnewtargetsforthetreatmentofgastriccancerisofgreatsignificance.ThisstudyaimedtoexploretheeffectofOridoninonthecellcycleofhumangastriccancerSGC-7901cellsinordertoprovidenewideasforthetreatmentofgastriccancer.

Inthisexperiment,SGC-7901cellswereselectedastheresearchobject.Throughcellexperiments,wefoundthatoridonincaninhibittheproliferationofSGC-7901cellsandcancausetheaccumulationofS-phaseandM-phasecells,indicatingthattheanti-tumoreffectoforidonininSGC-7901cellsmayberelatedtocellcycleregulation.FurtherstudieshaveshownthatoridonincanpreventSGC-7901cellsfromenteringthelaterstageofcytokinesis,inducecellapoptosis,andinhibittheproliferationoftumorcellsbyactivatingthemitogen-activatedproteinkinases(MAPKs)signalingpathway.

Therefore,weconcludethatoridonincaninhibittheproliferationofhumangastriccancerSGC-7901cells,anditsmechanismofactionmayberelatedtotheregulationofthecellcycleandtheactivationoftheMAPKssignalingpathway.Thisstudyrevealsthatoridonincanbeusedasapotentialdrugtargetforthetreatmentofgastriccancer,providingnewideasandmethodsforthetreatmentofgastriccancer.

Keywords:gastriccancer,SGC-7901cells,oridonin,cellcycle,MAPKssignalingpathwayGastriccancerisoneofthemostcommonmalignanciesworldwide,anditstreatmentremainsachallenge.OridoninisanaturalcompoundextractedfromRabdosiarubescenswithpotentialanticancereffects.Inthisstudy,weinvestigatedtheinhibitoryeffectoforidoninontheproliferationofhumangastriccancerSGC-7901cellsanditsunderlyingmechanism.

OurresultsshowedthatoridonininhibitedtheproliferationofSGC-7901cellsinadose-andtime-dependentmanner.FlowcytometryanalysisrevealedthatoridonininducedG2/Mphasearrestandincreasedthesub-G1populationinSGC-7901cells.WesternblotanalysisshowedthatoridonindownregulatedtheexpressionofcyclinB1andcyclin-dependentkinase1(CDK1),twoimportantproteinsregulatingtheG2/Mtransition.Furthermore,oridoninactivatedtheMAPKssignalingpathway,asevidencedbytheincreasedphosphorylationofextracellularsignal-regulatedkinase(ERK),c-JunN-terminalkinase(JNK),andp38MAPK.

ToconfirmtheroleoftheMAPKssignalingpathwayinoridonin-inducedcellcyclearrest,weusedspecificinhibitorsofERK,JNK,andp38MAPK.Ourresultsshowedthattheinhibitorspartiallyreversedoridonin-inducedG2/Mphasearrestanddecreasedthesub-G1population,suggestingthattheMAPKssignalingpathwaycontributestotheantiproliferativeeffectoforidonininSGC-7901cells.

Inconclusion,ourstudydemonstratesthatoridonininhibitstheproliferationofhumangastriccancerSGC-7901cells,anditsmechanismofactionmayberelatedtotheregulationofthecellcycleandtheactivationoftheMAPKssignalingpathway.Oridoninmayhavepotentialasatherapeuticagentforthetreatmentofgastriccancer,providingapotentialnewavenueforthedevelopmentofgastriccancertherapeuticsInadditiontoitsantiproliferativeeffectsongastriccancercells,oridoninhasalsobeenfoundtoexhibitanti-inflammatory,anti-tumor,andanti-metastaticactivitiesinothertypesofcancer,suchasbreastcancer,lungcancer,andleukemia.

OnestudyshowedthatoridonininhibitedtheproliferationofbreastcancercellsbyinducingapoptosisandcellcyclearrestattheG2/Mphase.Thiseffectwasmediatedbytheupregulationofp21andp27,whicharecyclin-dependentkinaseinhibitorsthatregulatethecellcycle.

Anotherstudyfoundthatoridoninsuppressedthegrowthandmetastasisoflungcancercellsbyinhibitingtheexpressionofmatrixmetalloproteinases(MMPs)andvascularendothelialgrowthfactor(VEGF),bothofwhichareinvolvedintumorinvasionandangiogenesis.

Furthermore,oridoninhasbeenshowntoenhancethesensitivityofcancercellstochemotherapydrugssuchasdoxorubicinandpaclitaxel.Thismaybeduetoitsabilitytoinhibittheexpressionofmultidrugresistanceproteins,whichareknowntoconferresistancetochemotherapydrugs.

Overall,thediversepharmacologicalactivitiesoforidoninmakeitapromisingcandidateforthedevelopmentofnewcancertherapeutics.FurtherstudiesareneededtoelucidateitsexactmolecularmechanismsofactionandtoevaluateitssafetyandefficacyinpreclinicalandclinicalsettingsInadditiontoitsanti-cancerproperties,oridoninhasalsoshownpotentialasatreatmentforotherdiseases.Forinstance,ithasbeenfoundtopossessanti-inflammatoryandimmunomodulatoryactivities.

Oridoninhasbeenshowntoreducetheproductionofpro-inflammatorycytokinessuchasTNF-alphaandinterleukin-6,andtoinhibittheactivityofnuclearfactor-kappaB(NF-kappaB),atranscriptionfactorthatplaysakeyroleintheregulationoftheimmuneresponseandinflammation.Thissuggeststhatoridoninmaybeusefulinthetreatmentofinflammatorydiseasessuchasrheumatoidarthritis,multiplesclerosis,andinflammatoryboweldisease.

Furthermore,oridoninhasbeenfoundtoenhancetheactivityofnaturalkiller(NK)cells,atypeofimmunecellthatplaysacrucialroleintherecognitionandeliminationofcancercellsandvirus-infectedcells.ThissuggeststhatoridoninmaybeusefulinthetreatmentofviralinfectionssuchasHIVandhepatitis,aswellasinthepreventionofcancermetastasis.

Inadditiontoitspharmacologicalactivities,oridoninhasalsoshownpromisingresultsinpreclinicalstudiesintermsofitspharmacokineticproperties.Ithasbeenfoundtohavegoodoralbioavailabilityandtoberapidlyabsorbedanddistributedthroughoutthebody.Moreover,ithasarelativelylonghalf-life,whichsuggeststhatitmayhaveaprolongedtherapeuticeffect.

However,furtherstudiesareneededtoexplorethefullpharmacologicalpotentialoforidonin,aswellastoevaluateitssafetyandefficacyinclinicaltrials.Someofthechallengesthatneedtobeaddressedincludeoptimizingitspharmacokineticproperties,identifyingthemosteffectivedosingregimens,andidentifyingpotentialdruginteractionsandsideeffects.

Inconclusion,oridoninisanaturalcompoundwithawider