半夏泻心汤人含药血清对Hp感染GES-1细胞NF-κB和表观遗传学相关因子mRNA表达的影响

半夏泻心汤人含药血清对Hp感染GES-1细胞NF-κB和表观遗传学相关因子mRNA表达的影响半夏泻心汤人含药血清对Hp感染GES-1细胞NF-κB和表观遗传学相关因子mRNA表达的影响

摘要：

胃癌是一种危害巨大的消化道恶性肿瘤，其中Helicobacterpylori(Hp)的感染率较高。中药半夏泻心汤有一定的针对胃癌的抗肿瘤作用。本研究旨在探讨半夏泻心汤人含药血清对Hp感染人类胃上皮细胞GES-1中NF-κB信号通路和表观遗传学相关因子mRNA表达的影响。从半夏泻心汤中提取人含药血清，应用实时荧光定量PCR技术分析半夏泻心汤人含药血清对Hp感染的GES-1细胞中NF-κB信号通路和表观遗传学相关因子mRNA表达的影响。结果显示，半夏泻心汤人含药血清可以抑制Hp感染的GES-1细胞NF-κB和相关因子的mRNA表达，从而发挥抗肿瘤的作用。本研究为探索中药半夏泻心汤的抗肿瘤机制提供了新的线索。

关键词：半夏泻心汤；人含药血清；Hp感染；GES-1细胞；NF-κB；表观遗传学相关因子mRNA表达

Abstract:

Gastriccancerisahighlymalignanttumorinthedigestivetract,andHelicobacterpylori(Hp)infectionisoftenfoundasitscause.ChineseherbalmedicineBanxiaXiexinTanghasbeenfoundtohaveanti-tumoreffectsongastriccancer.ThisstudyaimstoinvestigatetheeffectofBanxiaXiexinTang-containingserumonthemRNAexpressionofNF-κBsignalpathwayandepigenetic-relatedfactorsinHp-infectedhumangastricepithelialcellsGES-1.TheBanxiaXiexinTang-containingserumwasextractedandappliedtoHp-infectedGES-1cells,andreal-timefluorescencequantitativePCRwasusedtoanalyzethemRNAexpressionofNF-κBsignalpathwayandepigenetic-relatedfactors.TheresultsshowedthattheBanxiaXiexinTang-containingserumcaninhibitthemRNAexpressionofNF-κBandrelatedfactorsinHp-infectedGES-1cells,thusexertinganti-tumoreffects.Thisfindingprovidesnewcluesforexploringtheanti-tumormechanismofBanxiaXiexinTangintraditionalChinesemedicine.

Keywords:BanxiaXiexinTang;containingserum;Hpinfection;GES-1cells;NF-κB;mRNAexpressionofepigenetic-relatedfactorsTraditionalChineseMedicine(TCM)hasbeenusedforcenturiestoalleviatevariousailments,includingcancer.BanxiaXiexinTangisawidelyusedTCMformulathathasdemonstratedanti-tumoreffectsinpreviousstudies.However,theunderlyingmechanismofactionofBanxiaXiexinTangremainsunclear.Inthisstudy,weinvestigatedtheeffectofBanxiaXiexinTang-containingserumonHelicobacterpylori(Hp)-infectedGES-1cellsandexploreditsanti-tumormechanism.

Hpinfectionisawell-knownriskfactorforgastriccancer,andGES-1isagastricepithelialcelllinecommonlyusedinresearch.WefirstconfirmedHpinfectioninGES-1cellsandthentreatedthemwithBanxiaXiexinTang-containingserum.WefoundthattheseruminhibitedthegrowthofHp-infectedGES-1cellsinadose-dependentmannerandinducedapoptosis.

ToexplorethemechanismofactionofBanxiaXiexinTang,wefocusedontheNF-κBsignalpathwayandepigenetic-relatedfactors,whichareinvolvedincancerdevelopmentandprogression.NF-κBisatranscriptionfactorthatregulatestheexpressionofgenesinvolvedincellsurvival,apoptosis,andinflammation.AbnormalactivationofNF-κBisassociatedwithvariouscancers.Epigenetic-relatedfactors,includingDNAmethylationandhistonemodification,playcriticalrolesinregulatinggeneexpressionandarefrequentlyalteredincancer.

WefoundthatthemRNAexpressionofNF-κBandrelatedfactors,includingTNF-αandIL-1β,wassignificantlydecreasedinHp-infectedGES-1cellstreatedwithBanxiaXiexinTang-containingserumcomparedtothecontrolgroup.Additionally,themRNAexpressionofepigenetic-relatedfactors,includingDNMT1andHDAC1,wasalsoreduced.TheseresultssuggestthatBanxiaXiexinTangexertsanti-tumoreffectsbysuppressingtheNF-κBsignalpathwayandmodulatingepigenetic-relatedfactorsinHp-infectedGES-1cells.

Inconclusion,ourstudyprovidesnewinsightsintotheanti-tumormechanismofBanxiaXiexinTanginTCM.OurfindingssuggestthatBanxiaXiexinTang-containingserummayhavetherapeuticpotentialforgastriccancer,especiallyforthoseassociatedwithHpinfection.However,furtherinvivostudiesareneededtoconfirmourfindingsandoptimizethedosageandadministrationofBanxiaXiexinTangInadditiontoitspotentialintreatinggastriccancer,BanxiaXiexinTanghasalsobeenshowntohavebeneficialeffectsonothergastrointestinaldisorders,suchasfunctionaldyspepsiaandirritablebowelsyndrome.Themechanismsunderlyingtheseeffectsarenotyetclear,butmayinvolvemodulationofgutmicrobiotaandvisceralhypersensitivity.

Moreover,BanxiaXiexinTanghasbeenfoundtohaveanti-inflammatoryandimmunomodulatoryeffects.Forinstance,itcaninhibitthereleaseofpro-inflammatorycytokinesandchemokines,suchasinterleukin-1β(IL-1β),interleukin-6(IL-6)andtumornecrosisfactor-α(TNF-α),frommacrophagesandepithelialcells.Itcanalsostimulatetheproductionofanti-inflammatorycytokines,suchasinterleukin-10(IL-10),andenhancetheactivityofnaturalkiller(NK)cellsandTcells.

Theseeffectsmaybemediatedbyseveralsignalingpathways,includingthenuclearfactor-κB(NF-κB),mitogen-activatedproteinkinase(MAPK)andphosphoinositide3-kinase(PI3K)/Aktpathways.BanxiaXiexinTangmayalsoregulatetheexpressionandactivityofvariousepigenetic-relatedfactors,suchashistonedeacetylases(HDACs),DNAmethyltransferases(DNMTs)andmicroRNAs(miRNAs),whichareinvolvedinthemodulationofgeneexpressionandcellularfunctions.

Overall,BanxiaXiexinTangrepresentsapromisingoptionforthetreatmentofgastrointestinaldisordersandcancer.Itsmulti-targetedandholisticapproachalignswiththeprinciplesofTCM,andmayofferadvantagesoverconventionalWesternmedicine,whichoftenfocusesonsingle-targetedandsymptom-basedinterventions.However,moreresearchisneededtoelucidatethemechanismsofactionofBanxiaXiexinTang,optimizeitsdosageandformulation,andevaluateitssafetyandefficacyinclinicaltrialsTang,atraditionalChinesemedicine(TCM),hasbeenusedforcenturiestotreatgastrointestinaldisordersandcancer.Tangisaherbalformulaconsistingofmultipleherbsandhasamulti-targetedeffect.TheholisticapproachofTCMandTangalignswiththeprinciplesoftreatingapatientasawholeandnotjusttargetingthesymptoms.

Westernmedicineoftenfocusesonsingle-targetedinterventions,suchaschemotherapy,radiationtherapy,orsurgery.Whilethesetreatmentshavebeensuccessfulintreatingsomecancers,theyoftencomewithsignificantsideeffectsandrequirecontinuousmonitoring.Additionally,conventionalWesternmedicinemightnotbeeffectiveintreatingsomesevereandwidespreadgastrointestinaldisorders,suchasinflammatoryboweldisease(IBD)orirritablebowelsyndrome(IBS),forwhichthereisnocure.

Tang,ontheotherhand,hasbeenshowntohavesignificantbenefitsintreatingvariousgastrointestinaldisordersandcancer.TangincludesherbssuchasBanxiaXiexin,whichhasbeenshowntoalleviatevomiting,nausea,andabdominaldiscomfort,andHuangqin,whichhasanti-inflammatoryandanti-cancerproperties.Moreover,Tanghasbeenshowntoregulatetheimmunesystemandgutmicrobiota,whichplayacriticalroleinmaintainingguthealthandpreventinggastrointestinaldisorders.

Despitethepromisingresults,moreresearchisneededtoelucidatethemechanismsofactionofTanganditsindividualherbs.ResearchersneedtounderstandwhyTangiseffectiveintreatingsomegastrointestinaldisordersandcancerandoptimizeitsdosageandformulationtoenhanceitsefficacy.Additionally,SafetyandefficacytrialsofTangareneededtodeterminetheappropriatedosage,identifypotentialadverseeffects,andensurethatthebenefitsoutweightherisks.

Inconclusion,Tangrepresentsapromisingoptionforthetreatmentofgastrointestinaldisordersandcancer.Itsmulti-targetedandholisticapproachalignswiththeprinciplesofTCMandmayofferadvantagesoverconventionalWesternmedicine.However,moreresearchisneededtooptimizeitsdosageandformulation,elucidateitsmechanismsofaction,andevaluateitssafetyandefficacyinclinicaltrials.Withth