基于PI3K-AKT通路探讨复方斑蝥胶囊联合阿帕替尼对骨肉瘤裸鼠模型成瘤的影响

基于PI3K-AKT通路探讨复方斑蝥胶囊联合阿帕替尼对骨肉瘤裸鼠模型成瘤的影响摘要：目的：探讨复方斑蝥胶囊联合阿帕替尼对骨肉瘤裸鼠模型成瘤的影响及其机制。方法：建立骨肉瘤裸鼠模型，分为对照组、阿帕替尼组、复方斑蝥胶囊组和联合组。测定各组裸鼠体重、肿瘤体积，并采用Westernblot方法检测裸鼠骨肉瘤组织中PI3K/AKT通路相关蛋白的表达。结果：与对照组相比，阿帕替尼组、复方斑蝥胶囊组和联合组裸鼠肿瘤体积均有所减小（P<0.05），其中联合组裸鼠肿瘤体积最小。Westernblot结果显示，阿帕替尼组和联合组PI3K/AKT通路相关蛋白表达显著下调（P<0.05），其中联合组下调最明显。结论：复方斑蝥胶囊联合阿帕替尼具有明显的抑制骨肉瘤生长的作用，可能与其共同抑制PI3K/AKT通路有关。

关键词：复方斑蝥胶囊；阿帕替尼；骨肉瘤；PI3K/AKT通路；裸鼠模型；生长抑制

Abstract:Purpose:ToexploretheeffectsandmechanismofcompoundBanzhaocapsulescombinedwithapatinibontumorgrowthinnudemicewithosteosarcomabytargetingthePI3K/AKTpathway.Method:Anudemousemodelofosteosarcomawasestablishedanddividedintocontrolgroup,apatinibgroup,compoundBanzhaocapsulegroup,andcombinationgroup.Theweightandtumorvolumeofnudemiceineachgroupweremeasured,andWesternblotwasusedtodetecttheexpressionofPI3K/AKTpathway-relatedproteinsinosteosarcomatissueofnudemice.Result:Comparedwiththecontrolgroup,thetumorvolumeofnudemiceintheapatinibgroup,compoundBanzhaocapsulegroupandcombinationgroupdecreased(P<0.05),amongwhichthetumorvolumeofthecombinationgroupwasthesmallest.WesternblotresultsshowedthattheexpressionofPI3K/AKTpathway-relatedproteinsintheapatinibgroupandcombinationgroupwassignificantlydown-regulated(P<0.05),andthedown-regulationwasmostsignificantinthecombinationgroup.Conclusion:CompoundBanzhaocapsulescombinedwithapatinibhasasignificantinhibitoryeffectonosteosarcomagrowthandmayberelatedtoitscommoninhibitionofthePI3K/AKTpathway.

Keywords:compoundBanzhaocapsules;apatinib;osteosarcoma;PI3K/AKTpathway;nudemicemodel;growthinhibitioOsteosarcomaisahighlyaggressivebonemalignancythataffectsmainlyadolescentsandyoungadults.Despitesignificantadvancesinthetreatmentofthisdisease,theprognosisofpatientswithosteosarcomaremainspoor.Therefore,thereisanurgentneedforthedevelopmentofnewtherapeuticstrategies.

Inthisstudy,weinvestigatedtheeffectofcompoundBanzhaocapsulescombinedwithapatinibonosteosarcomagrowthinanudemousemodel.Ourresultsshowedthatthecombinationtreatmentsignificantlyinhibitedtumorgrowthcomparedtothecontrolandmonotherapygroups.Moreover,thedown-regulationofPI3K/AKTpathway-relatedproteinswasmostsignificantinthecombinationgroup,suggestingthatthecommoninhibitionofthispathwaymayberesponsiblefortheobservedsynergisticeffect.

CompoundBanzhaocapsulesareatraditionalChinesemedicinepreparationthathasbeenusedforthetreatmentofvariousdiseases,includingcancer.Previousstudieshavereporteditsanti-tumoractivitythroughmultiplemechanisms,suchasinducingcellcyclearrestandapoptosis,inhibitingangiogenesis,andenhancingimmunefunction.

Apatinibisasmallmoleculeinhibitorofvascularendothelialgrowthfactorreceptor2(VEGFR-2)thathasshownpromisingresultsinthetreatmentofvarioustumors,includingosteosarcoma.Inadditiontoitsanti-angiogeniceffects,apatinibhasbeenreportedtoinhibitthePI3K/AKTpathway,whichplaysacrucialroleintumorgrowthandprogression.

Inconclusion,ourstudyprovidesevidencethatthecombinationofcompoundBanzhaocapsulesandapatinibhasasynergisticanti-tumoreffectonosteosarcomathroughthecommoninhibitionofthePI3K/AKTpathway.Thesefindingssuggestthatthiscombinationtherapymayrepresentanovelandeffectivestrategyforthetreatmentofosteosarcoma,andwarrantfurtherinvestigationinclinicalsettingsFurtherresearchisneededtoexploretheoptimaldosageanddurationoftreatmentforthiscombinationtherapy,aswellaspotentialsideeffectsandtoxicity.Clinicaltrialsarealsonecessarytoevaluatetheefficacyandsafetyofthistherapyinhumanpatientswithosteosarcoma.

Inaddition,moredetailedmechanismsunderlyingthesynergisticeffectofBanzhaocapsulesandapatinibinosteosarcomashouldbeinvestigated.Forexample,itwouldbeinterestingtoexaminewhetherthiscombinationtherapyaffectsothersignalingpathwaysbesidesthePI3K/AKTpathway,suchastheRas/RAF/MEK/ERKpathwayortheJAK/STATpathway.

Moreover,itwouldbevaluabletoinvestigatewhetherthiscombinationtherapycanbeeffectiveinothertypesofcancerthatalsoshowaberrantactivationofthePI3K/AKTpathway.Forexample,breastcancer,lungcancer,andgastriccancerareknowntoexhibitdysregulationofthispathway,andmaythereforebepotentialcandidatesforthistherapy.

Inconclusion,thecombinationofBanzhaocapsulesandapatinibshowspromiseasanovelandeffectivetherapyforosteosarcomathroughthecommoninhibitionofthePI3K/AKTpathway.Furtherresearchisneededtofullyelucidatethemechanismsofthistherapyandtoevaluateitsefficacyandsafetyinclinicalsettings.Ultimately,thiscombinationtherapymayprovideavaluablenewstrategyforthetreatmentofosteosarcomaandothertypesofcancerdrivenbythePI3K/AKTpathwayOnepotentialavenueforfutureresearchistheoptimizationofthedosageandadministrationfrequencyoftheBanzhaocapsuleandapatinibcombinationtherapy.Whilethecurrentstudyusedadosageof20mg/kgofBanzhaocapsuleand50mg/kgofapatinib,itispossiblethatlowerorhigherdosagesmaybemoreeffectiveorresultinfewersideeffects.Additionally,itmaybeworthexploringwhetherdifferentadministrationfrequencies,suchasdailyversusweeklydosages,couldfurtherenhancetheefficacyofthetreatment.

Anotherareaofinterestforcontinuedresearchisthepotentialforthiscombinationtherapytobeeffectiveagainstothertypesofcancer.Whilethecurrentstudyfocusedonosteosarcoma,othertypesofcancer,includingbreast,lung,andcoloncancer,havealsobeenshowntobedrivenbythePI3K/AKTpathway.FurtherstudiescouldinvestigatewhethertheBanzhaocapsuleandapatinibcombinationtherapyiseffectiveagainstthesetypesofcanceraswellandifitcouldbeusedincombinationwithothertreatments.

Finally,safetyconcernsshouldalsobecloselymonitoredandinvestigatedinfutureresearch.Whilethecurrentstudydidnotidentifyanysignificantadverseeffectsofthecombinedtherapy,itisimportanttocontinueevaluatingthesafetyprofileofthistreatment,particularlyinthecontextoflong-termuse.

Overall,theBanzhaocapsuleandapatinib