生长抑素类似物对肝癌细胞的抑制作用及对CDK5表达的影响的综述报告

生长抑素类似物对肝癌细胞的抑制作用及对CDK5表达的影响的综述报告Abstract:Hepatocellularcarcinoma(HCC)isoneofthemostcommonmalignanttumors,anditsincidenceandmortalityratesareincreasingyearbyyear.AsanimportantmoleculartargetforthetreatmentofHCC,somatostatinanditsanalogueshavebeenwidelystudiedinrecentyears.Somatostatinisaneuropeptidethatcanregulatevariousphysiologicalfunctions,suchasinhibitingthereleaseofgrowthhormone,insulinandothermetabolichormonesfromthepituitaryglandandregulatinggastrointestinalmotility.Atthesametime,theuseofsomatostatinanaloguesforthetreatmentofHCChasalsobeenwidelystudied.Inthisarticle,theinhibitoryeffectofsomatostatinanaloguesonthegrowthoflivercancercellsandtheeffectontheexpressionofCDK5werereviewed.Introduction:Hepatocellularcarcinoma(HCC)isacommonmalignanttumoroftheliverandisoneoftheleadingcausesofcancer-relateddeathsworldwide.Itsincidenceandmortalityratesareincreasingyearbyyear.Atpresent,thetreatmentofHCCmainlyincludessurgicalresection,transplantation,radiotherapy,chemotherapyandmoleculartargetedtherapy.However,duetothehighheterogeneityofHCC,theeffectsofthesetreatmentmethodsarelimited,andtheprognosisofHCCpatientsisstillpoor.Therefore,thereisanurgentneedtoexplorenewmethodsforthetreatmentofHCC.Somatostatinisaneuropeptidethatcanregulatevariousphysiologicalfunctions,suchasinhibitingthereleaseofgrowthhormone,insulinandothermetabolichormonesfromthepituitaryglandandregulatinggastrointestinalmotility.Inrecentyears,somatostatinanditsanalogueshavebeenwidelystudiedasanimportantmoleculartargetforthetreatmentofHCC.EffectofsomatostatinanaloguesonHCCcellproliferation:Somatostatinanaloguesaresyntheticanaloguesofsomatostatin,whichhavealongerhalf-lifeandgreaterbioactivitythanthenaturalpeptide.PreviousstudieshaveshownthatsomatostatinanalogueshaveaninhibitoryeffectonthegrowthofHCCcells.Forexample,Lanreotide,asomatostatinanalogue,wasfoundtosignificantlyinhibittheproliferationofHCCcellsinvitrobyinducingS-phasearrestandinhibitingCyclinD1expression,andalsoreducedthegrowthofHCCxenograftsinnudemice.Octreotide,anothersomatostatinanalogue,alsohasaninhibitoryeffectonthegrowthofHCCcells.ItwasfoundthatOctreotideinhibitstheexpressionofVEGF,bFGF,andPDGFinHCCcells,whichinhibitstheangiogenesis,andpreventthegrowthofHCCcells.Themechanismofsomatostatinanalogues-mediatedgrowthinhibitionofHCCcells:ThemechanismbywhichsomatostatinanaloguesinhibitthegrowthofHCCcellsiscomplexandinvolvesmultiplesignalingpathways.StudieshaveshownthatthegrowthinhibitoryeffectofsomatostatinanaloguesonHCCcellsisrelatedtotheactivationofvariousintracellularsignalingpathways,theinhibitionofL-typecalciumchannels,andtheregulationofvarioustranscriptionfactors.ItwasfoundthatthedecreasedexpressionofCyclinD1andD2,andCDK4inhibitsthecellcycleprogressioninHCCcells.StudieshavealsoshownthatsomatostatinanaloguescaninhibittheexpressionandphosphorylationofAktandErkproteins,downregulatetheexpressionoftheanti-apoptoticproteinBcl-2,andupregulatetheexpressionoftheapoptoticproteinBax,leadingtotheinductionofapoptosisinHCCcells.EffectofsomatostatinanaloguesonCDK5expression:CDK5isaserine/threoninekinasethatishighlyexpressedinHCCtissuesandplaysanimportantroleinpromotingHCCcellproliferationandinvasion.StudieshaveshownthatsomatostatinanaloguescaninhibittheexpressionofCDK5inHCCcells,therebyinhibitingthegrowthandinvasionofHCCcells.Wangetal.foundthatSomatostatinanaloguesdecreasethephosphorylationofCDK5proteininvitro,resultinginthedecreasedmigratoryandinvasiveabilityofHCCcells.Moreover,theinhibitionofCDK5expressioncanalsoleadtothedownregulationofMMP-2andMMP-9expression,whichfurtheredtheinhibitoryeffectonHCCcellinvasion.Conclusion:Inconclusion,somatostatinanditsanalogueshavebeenfoundtohaveaninhibitoryeffectonHCCcellproliferationandinvasionandcandownregulatetheexpressionofCDK5,whichplaysanimportantroleinpromotingthegrowthandinvasionofHCC.Therefore,somatostatinanditsanaloguesmaybeapotentialtargetforthetreatmentofHCC,andfurtherresearchisnee