基于能量代谢体外研究白藜芦醇联用5-FU的抗肿瘤活性

基于能量代谢体外研究白藜芦醇联用5-FU的抗肿瘤活性摘要：本研究旨在探究白藜芦醇联用5-FU的抗肿瘤活性及其基于能量代谢的体外机制。采用MTT法检测不同浓度的白藜芦醇、5-FU及其联合用药对人结肠癌细胞系SW480的杀伤效应，同时测定药物对正常人肝细胞线L-02的影响。结果显示，联合用药对SW480细胞的抑制率高于单药组，且对L-02细胞影响较小。进一步研究发现，联合用药能够抑制细胞增殖、诱导细胞凋亡，并降低细胞膜通透性。同时，联合用药也能够影响细胞能量代谢，降低ATP水平，促进ROS产生，增强线粒体膜电位下降，诱导线粒体呼吸链复合体活性下降。以上结果表明，白藜芦醇联用5-FU能够发挥协同抗肿瘤效应，其机制与对能量代谢的影响密切相关。

关键词：白藜芦醇；5-FU；结肠癌细胞；能量代谢；线粒体

Abstract:Theaimofthisstudyistoinvestigatetheanti-tumoractivityofcombineduseofresveratroland5-FUanditsinvitromechanismbasedonenergymetabolism.MTTmethodwasusedtodetectthekillingeffectofdifferentconcentrationsofresveratrol,5-FUandtheircombinationonhumancoloncancercelllineSW480,andtheeffectofdrugsonnormalhumanlivercelllineL-02wasalsomeasured.TheresultsshowedthattheinhibitoryrateofcombinationtherapyonSW480cellswashigherthanthatofsingledruggroup,andithadlittleeffectonL-02cells.Furtherstudyfoundthatcombinedtherapycaninhibitcellproliferation,inducecellapoptosis,andreducecellmembranepermeability.Atthesametime,combinedtherapycanalsoaffectcellenergymetabolism,reduceATPlevel,promoteROSproduction,enhancemitochondrialmembranepotentialdecrease,andinducemitochondrialrespiratorychaincomplexactivitydecrease.Theaboveresultsindicatethatthesynergisticanti-tumoreffectofresveratrolcombinedwith5-FUiscloselyrelatedtoitseffectonenergymetabolism.

Keywords:resveratrol;5-FU;coloncancercells;energymetabolism;mitochondriInadditiontoaffectingenergymetabolism,thesynergisticanti-tumoreffectofresveratrolcombinedwith5-FUcanalsoinhibitcancercellproliferationandinduceapoptosis.StudieshaveshownthatresveratrolcaninhibittheexpressionofCyclinD1andpromotetheexpressionofp21andp27,whicharekeyregulatorsofcellcycleprogression.Moreover,resveratrolcanactivatecaspase-dependentandcaspase-independentapoptoticpathways,leadingtocancercelldeath.

Ontheotherhand,5-FUisacommonlyusedchemotherapeuticagentthatcanexertitsanti-tumoreffectbyinterferingwithDNAsynthesisandrepair,inhibitingcellproliferation,andinducingapoptosis.However,duetodrugresistanceandtoxicity,theclinicalapplicationof5-FUisstilllimited.Therefore,combining5-FUwithotheragentstoenhanceitseffectivenessandreduceitstoxicityisapromisingstrategyforcancertreatment.

Inconclusion,thecombinationofresveratroland5-FUcansynergisticallyinhibitcancercellproliferationandinduceapoptosisbyaffectingenergymetabolism,amongothermechanisms.Furtherstudiesareneededtoexploretheoptimaldoseandtreatmentregimenofthiscombinationtherapy,aswellasitssafetyandefficacyinclinicalsettingsOneareawherefurtherresearchisneededisintheidentificationofbiomarkersthatcanpredicttheresponseofcancercellstothecombinationofresveratroland5-FU.Thiscouldhelptopersonalizetreatmentplansandimproveoveralloutcomesforpatientswithcancer.

Additionally,theuseofresveratroland5-FUincombinationcouldhavepotentialbenefitsinthetreatmentofdifferenttypesofcancer,includingthosethatareresistanttostandardchemotherapyregimens.Sincebothoftheseagentshavemultiplemechanismsofaction,theycouldbeeffectiveintargetingcancercellsthathavedevelopedresistancetotraditionalcancertherapies.

Finally,itisalsoimportanttoconsiderthepotentialsideeffectsofthecombineduseofresveratroland5-FU,andtodetermineoptimaldosagesandtreatmentschedulesthatminimizetoxicitywhilemaintainingefficacy.Whileresveratrolisgenerallyconsideredsafe,highdosescancausegastrointestinalupsetandpotentiallyinterferewithbloodclotting.5-FUisknowntocausesideeffectssuchasnausea,vomiting,andhairloss,andcanalsoaffectthebonemarrow,leadingtoanemiaandincreasedriskofinfections.

Overall,thecombinationofresveratroland5-FUshowspromiseasapotentialcancertreatmentstrategy,butfurtherresearchisneededtofullyunderstanditsmechanismsofactionandtooptimizedosagesandtreatmentregimens.Withcontinuedinvestigation,itispossiblethatthiscombinationtherapycouldeventuallybecomeanimportanttoolinthefightagainstcancerInadditiontoitspotentialroleincancertreatment,resveratrolhasalsobeenstudiedforitshealthbenefitsinotherareas.Forexample,ithasbeenfoundtohaveanti-inflammatoryproperties,whichmaybeusefulinpreventingandtreatingchronicdiseasessuchasheartdisease,diabetes,andAlzheimer'sdisease.Resveratrolhasalsobeenshowntohaveantioxidantandanti-agingeffects,andmayhavepotentialasatreatmentforobesityandmetabolicdisorders.

Oneofthechallengesinstudyingresveratrolisitsrelativelylowbioavailability,meaningthatonlyasmallamountofthesubstanceisabsorbedbythebodywheningestedorally.Researchershavethereforelookedatalternativemethodsofdeliveringresveratrol,suchasthroughinjectionorinhalation,andhavealsoinvestigatedothercompoundsthatmayenhanceitsabsorptionandefficacy.

Overall,whiletheresearchonresveratrolisstillinitsearlystages,thecompoundshowspromiseasapotentialtreatmentforarangeofdiseases,includingcancer.Withcontinuedinvestigation,itispossiblethatthisnaturalcompoundcouldbecomeanimp