Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

Objective:ToinvestigatetheeffectsofE7080andN5-(1-iminoethyl)-L-ornithinedihydrochloride(L-NIO)oncolorectalcanceraloneandincombination.Methods:HT29colorectalcancercelllinefromSapInstitutewasused.Real-timecellanalysis(xCELLigencesystem)wasperformedtodeterminetheeffectsofE7080andL-NIOoncolorectalcellproliferation.WhileapoptosiswasdeterminedwithAnnexinVstaining,andtheeffectofagentsonangiogenesiswasdeterminedwithchorioallantoicmembrane(CAM)model.Results:WefoundthatE7080hasastrongantiproliferativeeffectwithanhalfmaximuminhibitionofconcentration(IC50)valueof5.60×10–8mol/L.AlsoithasbeenobservedthatE7080showedantiangiogenicandapoptoticeffectsonHT29colorectalcancercells.AntiangiogenicscoresofE7080were1.2,1.0and0.6for100,10and1nmol/LE7080concentrations,respectively.Furthermore,apoptosishasbeendetectedin71%ofHT29colorectalcancercellsafteradministrationof100nmol/LE7080whichmayindicatestrongapoptoticeffect.MeanwhileadministrationofL-NIOalonedidnotshowanyeffect,butthecombinationofE7080withL-NIOincreasedtheantiproliferative,antiangiogenicandapoptoticeffectsofE7080.Conclusions:ResultsofthisstudyindicatethatE7080maybeagoodchoiceintreatmentofcolorectaltumors.FurthermoretheincreasedeffectsofE7080whencombinedwithL-NIOraisethepossibilitytousealowerdoseofE7080andthereforeavoid/minimizethesideeffectsobservedwithE7080.