Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: non‐;    Hodgkin lymphoma;    Rho GTPase;    histone deacetylase inhibitor;    phosphoinositide 3‐;    kinase inhibitor;   

DOI  :  10.1189/jlb.2A0415-162R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Burkittlymphomaisahighlyaggressivenon‐HodgkinlymphomathatischaracterizedbyMYCderegulation.Recently,thePI3KpathwayhasemergedasacooperativeprosurvivalmechanisminBurkittlymphoma.Despitethehighlysuccessfulresultsoftreatmentthatusehigh‐dosechemotherapyregimensinpediatricBurkittlymphomapatients,thesurvivalrateofpediatricpatientswithprogressiveorrecurrentdiseaseislow.PI3Ksarealsoknowntoregulatecellmigration,andabnormalcellmigrationmaycontributetocancerprogressionanddisseminationinBurkittlymphoma.LittleisknownaboutBurkittlymphomacellmigration,butthecooperationbetweenMYCandPI3KinBurkittlymphomapathogenesissuggeststhatadrugcombinationcouldbeusedtotargetthedifferentstepsinvolvedinBurkittlymphomacelldisseminationanddiseaseprogression.TheaimofthisstudywastoinvestigatetheeffectsofthehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidcombinedwiththePI3KinhibitorLY294002onBurkittlymphomacellgrowthandmigration.Thecombinationenhancedthecellgrowthinhibitionandcell‐cyclearrestinducedbythePI3Kinhibitororhistonedeacetylaseinhibitorindividually.Moreover,histonedeacetylaseinhibitor/PI3KinhibitorcotreatmentsuppressedBurkittlymphomacellmigrationanddecreasedcellpolarization,AktandERK1/2phosphorylation,andleadstoRhoBinduction.Insummary,thehistonedeacetylaseinhibitor/PI3KicombinationinhibitscellproliferationandmigrationviaalterationsinPI3Ksignalingandhistonedeacetylaseactivity,whichisinvolvedintheacetylationofα‐tubulinandtheregulationofRhoBexpression...

【 授权许可】

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