基于能量代謝體外研究白藜蘆醇聯(lián)用5-FU的抗腫瘤活性

基于能量代謝體外研究白藜蘆醇聯(lián)用5-FU的抗腫瘤活性摘要：本研究旨在探究白藜蘆醇聯(lián)用5-FU的抗腫瘤活性及其基于能量代謝的體外機制。采用MTT法檢測不同濃度的白藜蘆醇、5-FU及其聯(lián)合用藥對人結(jié)腸癌細胞系SW480的殺傷效應(yīng)，同時測定藥物對正常人肝細胞線L-02的影響。結(jié)果顯示，聯(lián)合用藥對SW480細胞的抑制率高于單藥組，且對L-02細胞影響較小。進一步研究發(fā)現(xiàn)，聯(lián)合用藥能夠抑制細胞增殖、誘導(dǎo)細胞凋亡，并降低細胞膜通透性。同時，聯(lián)合用藥也能夠影響細胞能量代謝，降低ATP水平，促進ROS產(chǎn)生，增強線粒體膜電位下降，誘導(dǎo)線粒體呼吸鏈復(fù)合體活性下降。以上結(jié)果表明，白藜蘆醇聯(lián)用5-FU能夠發(fā)揮協(xié)同抗腫瘤效應(yīng)，其機制與對能量代謝的影響密切相關(guān)。

關(guān)鍵詞：白藜蘆醇；5-FU；結(jié)腸癌細胞；能量代謝；線粒體

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