辛二酰苯胺异羟肟酸联合紫杉醇对卵巢癌紫杉醇耐药细胞株的体外研究

辛二酰苯胺异羟肟酸联合紫杉醇对卵巢癌紫杉醇耐药细胞株的体外研究摘要：

本研究旨在探究辛二酰苯胺异羟肟酸联合紫杉醇对卵巢癌紫杉醇耐药细胞株的体外研究。本研究选取SKOV3/DDP细胞作为实验对象，通过MTT法检测不同浓度下药物对细胞的抑制率，同时采用流式细胞术检测细胞周期及凋亡率变化，WesternBlot检测相关蛋白的表达水平。结果显示，辛二酰苯胺异羟肟酸联合紫杉醇可协同作用，增强化疗效果；同时，该联合治疗能够诱导细胞周期G2/M期阻滞、增加细胞凋亡率、下调转录因子NF-κB和肿瘤耐药蛋白Bcl-2的表达水平。综上所述，辛二酰苯胺异羟肟酸联合紫杉醇可作为一种新型治疗卵巢癌紫杉醇耐药的药物方案，有望在临床应用中产生较好的疗效。

关键词：辛二酰苯胺异羟肟酸，紫杉醇，卵巢癌，耐药，MTT，细胞周期，凋亡，NF-κB，Bcl-2

Abstract:

Thepurposeofthisstudywastoinvestigatetheinvitroeffectsofoxaliplatinhydroxamicacidcombinedwithpaclitaxelonpaclitaxel-resistantovariancancercelllines.SKOV3/DDPcellswereselectedastheexperimentalobject,andtheinhibitoryrateofthedrugsonthecellsatdifferentconcentrationswastestedbyMTTmethod.Atthesametime,flowcytometrywasusedtodetectchangesincellcycleandapoptosisrate,andWesternBlotwasusedtodetecttheexpressionlevelsofrelatedproteins.Theresultsshowedthatthecombinationofoxaliplatinhydroxamicacidandpaclitaxelhadasynergisticeffect,whichenhancedthechemotherapyeffect.Meanwhile,thiscombinationtherapycouldinduceG2/Mphasearrest,increasetheapoptosisrate,anddownregulatetheexpressionlevelsoftranscriptionfactorNF-κBandtumorresistanceproteinBcl-2.Inconclusion,oxaliplatinhydroxamicacidcombinedwithpaclitaxelcanbeusedasanoveltreatmentforpaclitaxel-resistantovariancancer,whichisexpectedtoproducebettertherapeuticeffectsinclinicalapplication.

Keywords:oxaliplatinhydroxamicacid,paclitaxel,ovariancancer,drugresistance,MTT,cellcycle,apoptosis,NF-κB,Bcl-Introduction:

Ovariancancerisoneoftheleadingcausesofcancer-relateddeathsinwomenworldwide.Thestandardtreatmentforadvancedovariancancerincludessurgeryfollowedbycombinationchemotherapywithpaclitaxelandplatinumderivatives.However,thedevelopmentofdrugresistanceoftenleadstotreatmentfailureanddiseaserecurrence.Therefore,thereisanurgentneedforthedevelopmentofnewtreatmentstrategiestoovercomedrugresistanceandimprovepatientoutcomes.

Oxaliplatinhydroxamicacid:

Oxaliplatinhydroxamicacidisanovelplatinumderivativethatexhibitspotentanticanceractivityagainstabroadrangeofsolidtumors,includingovariancancer.ItactsbyinducingDNAdamage,leadingtocellcyclearrestandapoptosis.Furthermore,ithasbeenshowntoovercomeresistancetotraditionalplatinumcompounds,suchascisplatinandcarboplatin.Thus,ithasthepotentialtobeaneffectivetherapeuticagentinthetreatmentofovariancancer.

Combinationtherapy:

Combinationtherapywithoxaliplatinhydroxamicacidandpaclitaxelhasbeenshowntobesynergisticinpreclinicalstudies.Thiscombinationtargetsdifferentmechanismsofaction,resultinginamoreeffectiveandcomprehensivetreatmentstrategy.Additionally,ithasthepotentialtoovercomeresistancetopaclitaxelbyinhibitingtumorresistanceproteins.

Invitrostudies:

Invitrostudieshaveshownthatoxaliplatinhydroxamicacidcombinedwithpaclitaxelcaneffectivelyinhibitcellproliferationinpaclitaxel-resistantovariancancercelllines.ThiscombinationinducedcellcyclearrestattheG2/Mphaseandincreasedapoptosisrates.Furthermore,theexpressionlevelsoftranscriptionfactorNF-κBandtumorresistanceproteinBcl-2weredownregulated,indicatingapotentialmechanismforthesynergisticeffectofthiscombinationtherapy.

Conclusion:

Inconclusion,oxaliplatinhydroxamicacidcombinedwithpaclitaxelhasthepotentialtobeanoveltreatmentstrategyforpaclitaxel-resistantovariancancer.Invitrostudieshaveprovidedevidenceofitseffectivenessininhibitingcellproliferation,inducingcellcyclearrest,andpromotingapoptosis.FurtherstudiesareneededtoinvestigatetheclinicalefficacyandsafetyofthiscombinationtherapyinovariancancerFuturestudiesshouldalsoexplorethemolecularmechanismsunderlyingthesynergisticeffectofthiscombinationtherapy.Onepossiblemechanismisthemodulationofthemicrotubulenetwork.Paclitaxelstabilizesmicrotubules,whileoxaliplatininterfereswithmicrotubuledynamics.Thecombinedeffectofthesetwodrugscoulddisruptthemicrotubulenetworkandcausecelldeath.Anotherpossiblemechanismistheupregulationofreactiveoxygenspecies(ROS)levels.BothpaclitaxelandoxaliplatinareknowntoinduceROSgeneration,whichcanleadtomitochondrialdysfunctionandapoptosis.

Inadditiontoovariancancer,thiscombinationtherapymayalsobeeffectiveinothertypesofcancer,suchasbreastcancer,lungcancer,andgastriccancer.Paclitaxelandoxaliplatinarebothcommonlyusedchemotherapydrugsandhavebeenextensivelystudiedincombinationwithotheragents.Somestudieshaveshownpromisingresultsinothercancertypes,suggestingthatthiscombinationtherapycouldhavebroadapplicabilityinoncology.

Insummary,thecombinationofoxaliplatinhydroxamicacidandpaclitaxelhasthepotentialtoovercomepaclitaxelresistanceinovariancancer.Invitrostudieshavedemonstrateditseffectivenessininhibitingcellproliferation,inducingcellcyclearrest,andpromotingapoptosis.Futurestudiesareneededtoinvestigatetheclinicalefficacyandsafetyofthiscombinationtherapyinovariancancerandothercancertypes,aswellastheunderlyingmolecularmechanisms.Ifsuccessful,thiscombinationtherapycouldprovideanewtreatmentstrategyforpatientswithcancerwhohavedevelopedresistancetochemotherapyInadditiontoitspotentialanticancereffects,curcuminhasalsobeenfoundtohaveanti-inflammatory,antioxidant,andneuroprotectiveproperties.Thesepropertiesmakeitapromisingcandidateforthetreatmentofvariousdiseases,includingAlzheimer'sdisease,Parkinson'sdisease,andmultiplesclerosis.

Oneofthemainchallengesintheuseofcurcuminasatherapeuticagentisitspoorbioavailability.Curcuminhaslowsolubilityandstabilityinwater,andisrapidlymetabolizedandexcretedfromthebody.Anumberofapproacheshavebeenusedtoimprovethepharmacokineticsofcurcumin,includingtheuseofnanoparticleformulations,liposomes,andotherdeliverysystems.

Recentstudieshavealsoexploredtheuseofcurcuminincombinationwithotheragentstoachievesynergisticeffects.Forexample,thecombinationofcurcuminwithresveratrol,apolyphenolfoundingrapesandredwine,hasbeenshowntohaveanti-inflammatory,anti-tumor,andanti-agingeffectsinvitroandinvivo.Otherstudieshaveinvestigatedtheuseofcurcuminincombinationwithvitamins,minerals,andothernaturalcompounds.

Inconclusion,curcuminisanaturalcompoundwithpromisinganticancerpropertiesthathasbeenextensivelystudiedinpreclinicalandclinicalsettings.Whileitsuseasamonotherapyforcancertreatmenthasbeenlimitedbyitspoorbioavailability,rec