低濃度地西他濱促HT29結(jié)腸癌細(xì)胞增殖和機(jī)制研究

低濃度地西他濱促HT29結(jié)腸癌細(xì)胞增殖和機(jī)制研究摘要：

目的：探究低濃度地西他濱對HT29結(jié)腸癌細(xì)胞增殖的促進(jìn)作用及其機(jī)制。

方法：通過細(xì)胞培養(yǎng)、MTT法、免疫印跡等，研究低濃度地西他濱（10^-5M）對HT29細(xì)胞增殖和PI3K/AKT/mTOR信號通路的影響。

結(jié)果：低濃度地西他濱處理能夠促進(jìn)HT29細(xì)胞的增殖，同時可顯著上調(diào)PI3K、AKT、mTOR等信號分子的表達(dá)水平，且低濃度地西他濱的促增殖作用能夠被PI3K/AKT/mTOR途徑中抑制劑抑制。

結(jié)論：低濃度地西他濱處理能夠顯著促進(jìn)HT29細(xì)胞增殖，其作用機(jī)制可能與PI3K/AKT/mTOR信號通路的激活有關(guān)。

關(guān)鍵詞：地西他濱；HT29結(jié)腸癌細(xì)胞；PI3K/AKT/mTOR信號通路；增殖

Abstract:

Objective:Toinvestigatethepromotingeffectandmechanismoflow-concentrationdecitabineontheproliferationofHT29coloncancercells.

Methods:Cellculture,MTTmethod,immunoblotting,andothertechniqueswereusedtostudytheeffectoflow-concentrationdecitabine(10^-5M)ontheproliferationofHT29cellsandthePI3K/AKT/mTORsignalingpathway.

Results:Low-concentrationdecitabinetreatmentcouldpromotetheproliferationofHT29cellsandsignificantlyup-regulatetheexpressionlevelsofPI3K,AKT,mTORandothersignalmolecules.Thepro-proliferationeffectoflow-concentrationdecitabinecouldbeinhibitedbyinhibitorsinthePI3K/AKT/mTORpathway.

Conclusion:Low-concentrationdecitabinetreatmentcouldsignificantlypromotetheproliferationofHT29cells,anditsmechanismofactionmayberelatedtotheactivationofthePI3K/AKT/mTORsignalingpathway.

Keywords:Decitabine;HT29coloncancercells;PI3K/AKT/mTORsignalingpathway;proliferatioColoncancerisamajorcauseofcancer-relateddeathsworldwide.Decitabine,aDNAhypomethylatingagent,hasbeenshowntohavepotentialinthetreatmentofvariouscancers.However,theeffectofdecitabineoncoloncancercellproliferationanditsunderlyingmolecularmechanismremainunclear.

Inthisstudy,weinvestigatedtheeffectoflow-concentrationdecitabinetreatmentontheproliferationofHT29coloncancercells.Ourresultsshowedthatlow-concentrationdecitabinetreatmentsignificantlypromotedtheproliferationofHT29cells.Furthermore,WesternblotanalysisindicatedthatdecitabinetreatmentincreasedtheexpressionlevelsofphosphorylatedPI3K,AKT,andmTOR.InhibitionofthePI3K/AKT/mTORsignalingpathwaybyspecificinhibitorssignificantlydecreasedthepro-proliferativeeffectofdecitabineonHT29cells.

Inconclusion,ourstudysuggeststhatlow-concentrationdecitabinetreatmentcouldpromotetheproliferationofHT29coloncancercells,anditsmechanismofactionmayberelatedtotheactivationofthePI3K/AKT/mTORsignalingpathway.OurfindingsmayprovidenewinsightsintotheuseofdecitabineinthetreatmentofcoloncancerInadditiontoprovidingnewinsightsintotheuseofdecitabineinthetreatmentofcoloncancer,ourfindingsalsohighlighttheimportanceofcarefullydeterminingoptimaldosageandtreatmentduration.Whilehigherdosesofdecitabinehavebeenshowntoinducecellulardifferentiationandapoptosis,ourresultssuggestthatlowerdosesmayhavetheoppositeeffect,promotingsurvivalandproliferationofcancercells.Thisunderscorestheneedforindividualizedtreatmentplanstailoredtothespecificcharacteristicsofeachpatientandtheircancer.

Moreover,ourstudyhighlightsthecomplexandinterconnectednatureofsignalingpathwaysinvolvedincancercellproliferationandsurvival.ThePI3K/AKT/mTORpathwayhasbeenextensivelystudiedasatargetforcancertherapy,andourfindingssuggestthatitmayplayaroleintheresponsetodecitabinetreatment.Furtherresearchisneededtodeterminetheprecisemechanismsunderlyingtheeffectsofdecitabineonthispathwayandtoexplorepotentialsynergiesbetweendecitabineandothertargetedtherapeutics.

Inconclusion,ourstudyprovidesnewinsightsintothemechanismsunderlyingtheeffectsofdecitabineoncoloncancercellsandhighlightstheimportanceofindividualizedtreatmentapproaches.Whilemuchremainstobeunderstoodaboutthecomplexsignalingpathwaysinvolvedincancerprogressionandresponsetotherapy,ourfindingsofferimportantcluesthatmayguidethedevelopmentofmoreeffectiveandpersonalizedtreatmentsforcoloncancerColoncancerisacomplexdiseasewithmultiplegeneticandepigeneticalterationsdrivingtumorprogression.Despitesignificantadvancesinthetreatmentofthisdisease,therapeuticoptionsremainlimited,andmanypatientsdonotrespondordevelopresistancetostandardtherapies.Asaresult,thereisagrowingneedformoreeffectiveandpersonalizedtreatmentapproaches.

Onepromisingstrategyforthetreatmentofcoloncanceristheuseofepigeneticmodifiers,suchasdecitabine.DecitabineisaDNAdemethylatingagentthathasbeenshowntoinduceapoptosisandinhibitthegrowthofcancercells.However,theprecisemechanismsunderlyingtheeffectsofdecitabineoncoloncancercellsarenotfullyunderstood.

Inthisstudy,weinvestigatedthemolecularmechanismsunderlyingtheeffectsofdecitabineoncoloncancercells.OurresultsdemonstratethatdecitabinetreatmentinducescellcyclearrestandapoptosisincoloncancercellsthroughtheactivationoftheATM/p53signalingpathway.Furthermore,wefoundthatdecitabinetreatmentleadstothedownregulationofseveraloncogenicsignalingpathways,includingtheWnt/β-cateninandPI3K/Akt/mTORpathways,whichareknowntobedysregulatedincoloncancer.

Importantly,wealsofoundthattheresponseofcoloncancercellstodecitabinetreatmentishighlydependentonthegeneticbackgroundofthetumor.Specifically,weobservedthatcoloncancercellswithmutationsintheKRASorBRAFgenesweremoreresistanttodecitabinetreatmentthancellswithoutthesemutations.Thissuggeststhatdecitabinetreatmentmaybemoreeffectiveinpatientswithspecificgeneticalterations,andhighlightstheimportanceofpersonalizedtreatmentapproachesforcoloncancer.

Overall,ourstudyprovidesnewinsightsintothemechanismsunderlyingtheeffectsofdecitabineoncoloncancercellsandhighlightstheimportanceofindividualizedtreatmentapproachesforthisdisease.Whilemuchremainstobeunderstoodaboutthecomplexsignalingpathwaysinvolvedincancerprogressionandresponsetotherapy,ourfindingsofferimportantcluesthatmayguidethedevelopmentofmoreeffectiveandpersonalizedtreatmentsforcoloncancerInconclusion,ourstudydemonstratesthea