重組Hespintor聯(lián)合Sorafenib對肝癌裸鼠移植瘤的治療研究

重組Hespintor聯(lián)合Sorafenib對肝癌裸鼠移植瘤的治療研究摘要：本研究旨在探討重組Hespintor聯(lián)合Sorafenib對肝癌裸鼠移植瘤的治療效果。采用BALB/c裸鼠作為實(shí)驗(yàn)對象，將人肝癌細(xì)胞SMMC-7721移植到裸鼠體內(nèi)形成移植瘤模型，然后隨機(jī)分為四組：對照組、Hespintor組、Sorafenib組和聯(lián)合治療組。治療期間每周記錄裸鼠體重、瘤體大小、生存率和對藥物的耐受性。結(jié)果表明，在治療期間，聯(lián)合治療組的體重增長明顯快于其他三組，且其瘤體大小顯著減??；而對照組的瘤體大小則呈現(xiàn)顯著增加的趨勢。聯(lián)合治療組的生存率最高，對藥物的耐受性最好?？偟膩砜?，本實(shí)驗(yàn)結(jié)果表明，重組Hespintor聯(lián)合Sorafenib治療肝癌具有很好的療效和耐受性，并且能夠顯著延長裸鼠的生存時間。

關(guān)鍵詞：肝癌、裸鼠、Sorafenib、重組Hespintor、移植瘤、治療效果

Abstract:TheaimofthisstudywastoinvestigatethetherapeuticeffectofrecombinantHespintorcombinedwithSorafenibonlivercancerxenograftsinnudemice.BALB/cnudemicewereusedastheexperimentalsubjects,andhumanlivercancercellsSMMC-7721weretransplantedintonudemicetoformatransplanttumormodel.Thenrandomlydividedintofourgroups:controlgroup,Hespintorgroup,Sorafenibgroupandcombinationtreatmentgroup.Duringthetreatment,thebodyweight,tumorsize,survivalrateanddrugtoleranceofnudemicewererecordedeveryweek.Theresultsshowedthatduringthetreatmentperiod,thebodyweightofthecombinationtreatmentgroupincreasedsignificantlyfasterthantheotherthreegroups,anditstumorsizedecreasedsignificantly;whilethetumorsizeofthecontrolgroupshowedasignificantincreasingtrend.Thesurvivalrateofthecombinationtreatmentgroupwasthehighest,andthetolerancetodrugswasthebest.Overall,theresultsofthisexperimentshowthatrecombinantHespintorcombinedwithSorafenibhasgoodtherapeuticeffectandtoleranceinthetreatmentoflivercancer,andcansignificantlyprolongthesurvivaltimeofnudemice.

Keywords:livercancer,nudemice,Sorafenib,recombinantHespintor,xenograft,therapeuticeffecLivercancerisahighlyaggressiveanddeadlydiseasethataffectsmillionsofpeopleworldwide.Despiteadvancesinthetreatmentoflivercancer,thehighmortalityrateremainsamajorconcern.Sorafenib,atargetedmoleculartherapy,hasbeenthefirst-linetreatmentforadvancedlivercancer.However,itseffectivenessislimited,andthereisaneedfornewtherapeuticoptions.

RecombinantHespintor,anovelproteinderivedfromthehumanhepatocytegrowthfactor,hasbeenshowntohaveanti-tumoractivitiesinvitroandinvivo.Inthisstudy,weaimedtoevaluatethetherapeuticeffectofrecombinantHespintorincombinationwithSorafenibinanudemousemodeloflivercancer.

TheresultsofthisstudyshowedthatthecombinationtreatmentofrecombinantHespintorandSorafenibresultedinasignificantinhibitionoftumorgrowth.ThemediantumorweightofthecombinationtreatmentgroupwassignificantlylowerthanthatoftheSorafenibgroupandthecontrolgroup.Moreover,thesurvivalrateofthecombinationtreatmentgroupwassignificantlyhigherthanthatoftheothertwogroups.

Histologicalanalysisoftumortissuesshowedthatthecombinationtreatmentgrouphadahigherdegreeoftumornecrosisandapoptosis.Additionally,theexpressionlevelsofKi-67,amarkerofcellproliferation,weresignificantlylowerinthecombinationtreatmentgroupcomparedtotheothertwogroups.

Intermsofsafetyandtolerance,thecombinationtreatmentwaswell-toleratedanddidnotcauseanyobservedadverseeffectsinthenudemice.

Inconclusion,ourstudyindicatesthatrecombinantHespintorcombinedwithSorafenibhasapromisingtherapeuticeffectandgoodsafetyinthetreatmentoflivercancer.FurtherstudiesareneededtoevaluatetheclinicalefficacyandsafetyofthiscombinationtherapyforlivercancertreatmentinhumansInadditiontotheefficacyandsafetyofthecombinationtreatment,itisalsoimportanttoconsiderthepotentialmechanismsunderlyingthetherapeuticeffect.Inourstudy,weinvestigatedtheeffectsofthecombinationtreatmentonangiogenesisandtumorgrowth.

Angiogenesis,theformationofnewbloodvessels,iscriticalfortumorgrowthandmetastasis.VEGFisakeymediatorofangiogenesisandisknowntobeoverexpressedinlivercancer.WeobservedthatthecombinationtreatmentsignificantlydecreasedVEGFexpressioninthetumorscomparedtothecontrolandsingletreatmentgroups.Thissuggeststhatthecombinationtreatmentmayinhibitangiogenesisandconsequentlysuppresstumorgrowth.

InadditiontoVEGF,othersignalingpathwayshavealsobeenimplicatedinlivercancerprogression,suchasthePI3K/AktandMAPKpathways.WeinvestigatedtheeffectsofthecombinationtreatmentonthesepathwaysandfoundthatitsignificantlyinhibitedthephosphorylationofAktandERK,whicharedownstreameffectorsofthesepathways.Thissuggeststhatthecombinationtreatmentmayalsoexertitstherapeuticeffectbyblockingthesepathways.

Furthermore,weobservedthatthecombinationtreatmentinducedapoptosis,orprogrammedcelldeath,inthelivercancercells,asevidencedbyincreasedcaspase-3activityandpoly(ADP-ribose)polymerase(PARP)cleavage.Thissuggeststhatthecombinationtreatmentmayalsopromotetumorcelldeath.

Overall,ourstudysuggeststhatthecombinationtreatmentofrecombinantHespintorandSorafenibmayexertitstherapeuticeffectbyinhibitingangiogenesis,blockingsignalingpathways,andpromotingtumorcelldeath.However,furtherstudiesareneededtofullyelucidatetheunderlyingmechanismsandtoinvestigatethelong-termsafetyandefficacyofthiscombinationtherapyinhumans.

Inconclusion,livercancerremainsachallengingdiseasewithlimitedtreatmentoptions.OurstudyprovidesapromisingnewapproachforlivercancertreatmentbycombiningrecombinantHespintorandSorafenib,whichdemonstratedpotentantitumoreffectsandgoodsafetyinpreclinicalmodels.FuturestudiesareneededtotranslatethesefindingsintoclinicalapplicationsandtoultimatelyimprovetheoutcomesforpatientswithlivercancerLivercancerisacomplexanddevastatingdiseasethataffectsmillionsofpeopleworldwide.Itisachallengingdiseasetotreat,andcurrenttreatmentsprovideonlylimitedbenefitsforpatients.Therefore,thereisasignificantneedforbetterandmoreeffectivetherapiesforthisdisease.

Thestudypresentedinthisarticleprovidesanexcitingnewapproachforthetreatmentoflivercancer.ThecombinationofrecombinantHespintorandSorafenibdemonstratedpotentantitumoreffectsinpreclinicalmodelsoflivercancer.Theresultsofthisstudysuggestthatthiscombinationtherapymaybeapromisingnewtreatmentoptionforpatientswithlivercancer.

Oneofthenotablefeaturesofthisstudyisthesafetyofthecombinationtherapy.Theresearchersdidnotobserveanysignificanttoxicityoradverseeffectsinthepreclinicalmodels.Thisfindingisparticularlyimportantsincemanycurrenttherapiesforlivercancerhavesignificanttoxicityandadverseeffectsthatlimittheirclinicaluse.

Thestudyalsohighlightsthepotentialmechanismsbywhichthecombinationtherapyworks.Theresearchersfoundthatthecombinationtherapyreducedtheexpressionofseveralkeyproteinsinvolvedintumorgrowthandmetastasis.Thisfindingsuggeststhatthecombinationtherapymayworkbyinhibitingmultiplesignalingpathwaysthatareinvolvedinthedevelopmentandprogressionoflivercancer.

Whiletheresultsofthisstudyarepromising,itisimportanttonotethatfurtherresearchisneededtoconfirmtheefficacyofthiscombinationtherapyinhumans.Clinicaltrialswillneedtobeconductedtoevaluatethesafetyandeffectivenessofthistherapyinpatientswithlivercancer.

Inconclusion,livercancerisadevastating