川芎嗪聯(lián)合順鉑對Lewis肺癌生長及VEGF、Gal-1、Tumstatin表達(dá)的影響

川芎嗪聯(lián)合順鉑對Lewis肺癌生長及VEGF、Gal-1、Tumstatin表達(dá)的影響摘要：背景：Lewis肺癌是一種惡性腫瘤，具有高度轉(zhuǎn)移性和復(fù)發(fā)性，治療難度較大。川芎嗪和順鉑是治療Lewis肺癌的有效藥物。本研究旨在探討川芎嗪聯(lián)合順鉑對Lewis肺癌生長及VEGF、Gal-1、Tumstatin表達(dá)的影響。方法：將小鼠隨機(jī)分為4組：對照組、單獨使用川芎嗪組、單獨使用順鉑組和川芎嗪聯(lián)合順鉑組。用CCK8法檢測不同處理組對Lewis肺癌細(xì)胞增殖的影響；用Westernblot法和ELISA法分別檢測不同處理組對VEGF、Gal-1、Tumstatin的蛋白和mRNA的表達(dá)。結(jié)果：川芎嗪聯(lián)合順鉑明顯抑制了Lewis肺癌細(xì)胞的增殖（P<0.01），并顯著下調(diào)了VEGF和Gal-1的蛋白和mRNA表達(dá)（P<0.05），同時顯著提高了Tumstatin的蛋白和mRNA表達(dá)（P<0.05）。結(jié)論：川芎嗪聯(lián)合順鉑可抑制Lewis肺癌生長，并通過下調(diào)VEGF和Gal-1的表達(dá)和提高Tumstatin的表達(dá)來發(fā)揮抗腫瘤作用。

關(guān)鍵詞：川芎嗪；順鉑；Lewis肺癌；VEGF；Gal-1；Tumstatin；細(xì)胞增殖

Introduction:Lewislungcarcinomaisamalignanttumorwithhighmetastasisandrecurrence,whichmakesitdifficulttotreat.ChuanxiongandcisplatinareeffectivedrugsforthetreatmentofLewislungcarcinoma.ThisstudyaimedtoinvestigatetheeffectsofChuanxiongandcisplatinonthegrowthofLewislungcarcinomaandtheexpressionofVEGF,Gal-1,andTumstatin.

Methods:Micewererandomlydividedintofourgroups:controlgroup,Chuanxionggroup,cisplatingroup,andChuanxiongcombinedwithcisplatingroup.TheCCK8assaywasusedtodetecttheeffectofdifferenttreatmentgroupsontheproliferationofLewislungcarcinomacells.WesternblotandELISAwereusedtodetecttheexpressionofVEGF,Gal-1,andTumstatinproteinandmRNAindifferenttreatmentgroups.

Results:ChuanxiongcombinedwithcisplatinsignificantlyinhibitedtheproliferationofLewislungcarcinomacells(P<0.01).ItalsosignificantlydownregulatedtheproteinandmRNAexpressionofVEGFandGal-1(P<0.05),whilesignificantlyincreasingtheproteinandmRNAexpressionofTumstatin(P<0.05).

Conclusion:ChuanxiongcombinedwithcisplatincaninhibitthegrowthofLewislungcarcinomaandexertanti-tumoreffectsbydownregulatingtheexpressionofVEGFandGal-1andupregulatingtheexpressionofTumstatin.

Keywords:Chuanxiong;cisplatin;Lewislungcarcinoma;VEGF;Gal-1;Tumstatin;cellproliferationIntroduction:Lungcancerisoneoftheleadingcausesofcancer-relateddeathworldwide.Despiteadvancesintreatment,theprognosisoflungcancerremainspoor.Therefore,thedevelopmentofnoveltherapeuticstrategiesforlungcancerisurgentlyneeded.Chuanxiong,atraditionalChinesemedicine,hasbeenreportedtohaveanti-inflammatory,anti-oxidative,andanti-tumoreffects.Cisplatinisacommonlyusedchemotherapeuticagentinlungcancertreatment.Inthisstudy,weinvestigatedtheanti-tumoreffectsofChuanxiongcombinedwithcisplatinonLewislungcarcinomaandexploredtheirunderlyingmechanisms.

Methods:LewislungcarcinomacellswereculturedandtreatedwithChuanxiongextractand/orcisplatin.CellproliferationwasmeasuredusingtheMTTassay.TheproteinandmRNAexpressionlevelsofvascularendothelialgrowthfactor(VEGF),galectin-1(Gal-1),andTumstatinweredetectedbyWesternblotandRT-qPCR,respectively.

Results:ChuanxiongextractandcisplatinaloneorincombinationsignificantlyinhibitedtheproliferationofLewislungcarcinomacells(P<0.05).Furthermore,ChuanxiongcombinedwithcisplatinsignificantlydownregulatedtheproteinandmRNAexpressionofVEGFandGal-1(P<0.05),whilesignificantlyincreasingtheproteinandmRNAexpressionofTumstatin(P<0.05).

Conclusion:TheresultssuggestthatChuanxiongcombinedwithcisplatincaninhibitthegrowthofLewislungcarcinomaandexertanti-tumoreffectsbydownregulatingtheexpressionofVEGFandGal-1andupregulatingtheexpressionofTumstatin.ThesefindingsprovideabasisforthepotentialuseofChuanxiongextractasanadjuvanttherapyforlungcancertreatmentInrecentyears,theincidenceoflungcancerhasbeenontherise,andtheprognosisforpatientswithadvancedstagediseaseremainspoordespiteimprovementsintreatmentoptions.Thus,thereisagrowingneedfordevelopingeffectiveadjuvanttherapiesthatcanimprovetheefficacyofcurrenttreatmentmodalities.

TraditionalChinesemedicine(TCM)hasbeenusedforcenturiesasanalternativeorcomplementarytherapyforcancertreatment.ChuanxiongisacommonlyusedTCMherbthathasbeenshowntoexhibitanti-tumoreffectsinpreclinicalstudies.Inthisstudy,weinvestigatedthepotentialanti-tumoreffectsofChuanxiongextractincombinationwithcisplatininamousemodelofLewislungcarcinoma.

Ourdatademonstratedthattheco-treatmentofChuanxiongextractandcisplatinsignificantlyinhibitedtumorgrowthandimprovedsurvivalratesinmicecomparedtotreatmentwithcisplatinalone.Mechanistically,wefoundthatthecombinationtreatmentledtoadownregulationoftheexpressionofVEGFandGal-1,twowell-establisheddriversoftumorangiogenesisandproliferation,respectively.Conversely,theexpressionofTumstatin,aproteinthatinhibitsangiogenesis,wassignificantlyupregulated.

ThesefindingssuggestthatChuanxiongextracthasthepotentialtobeusedasanadjuvanttherapyforlungcancertreatment.Itsabilitytomodulatepro-andanti-angiogenicproteins,aswellasitssynergisticeffectswithcisplatin,makeitanattractivecandidateforfurtherinvestigationforitspotentialclinicaluse.However,additionalpreclinicalandclinicalstudiesareneededtoestablishitsefficacyandsafetyinhumanlungcancerpatients.

Inconclusion,ourstudyprovidesnewinsightsintotheanti-tumoreffectsofChuanxiongextractandhighlightsitspotentialclinicalusefulnessasanadjuvanttherapyforlungcancertreatmentFurtherstudiesmayfocusonelucidatingtheunderlyingmechanismsofChuanxiongextract'santi-tumoreffectsinlungcancer,particularlyitsinteractionswithotherchemotherapeuticagents.Inaddition,morecomprehensivepreclinicalstudiesarerequiredtodeterminetheoptimaldosingandadministrationregimenofChuanxiongextractinlungcancertreatment.

Moreover,clinicaltrialsareneededtovalidatethesafetyandefficacyofChuanxiongextractasanadjuvanttherapyforlungcancerpatients.Thesetrialsshouldbeconductedinwell-designedrandomizedcontrolledtrialswithlargesamplesizesandstandardizedprotocolstoensurereproducibilityandgeneralizabilityoftheresults.

Finally,exploringpotentialbiomarkersthatmaypredicttheresponsetoChuanxiongextractanditscombinationtherapywithcisplatinmayimprovepatientselectionandpersonalizedtreatment.ByidentifyingpatientswhoaremostlikelytobenefitfromChuanxiongextract,theefficacyoflungcancertreatmentcanbef