Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer 英文参考文献.docVIP
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Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer 英文参考文献
AntitumorActivityofNoscapineinCombinationwith
DoxorubicininTripleNegativeBreastCancer
MahavirB.Chougule1,ApurvaR.Patel2,TaniseJackson2,MandipSingh2*
1CollegeofPharmacy,UniversityofHawaii,Hilo,Hawaii,UnitedStatesofAmerica,2CollegeofPharmacy,FloridaAMUniversity,Tallahassee,Florida,UnitedStatesof
America
Abstract
Background:TheaimofthisstudywastoinvestigatetheanticanceractivityandmechanismofactionofNoscapinealone
andincombinationwithDoxorubicinagainsttriplenegativebreastcancer(TNBC).
Methods:TNBCcellswerepretreatedwithNoscapineorDoxorubicinorcombinationandcombinationindexvalueswere
calculated using isobolographic method. Apoptosis was assessed by TUNEL staining. Female athymic Nu/nu mice were
xenograftedwithMDA-MB-231cellsandtheefficacyofNoscapine,Doxorubicinandcombinationwasdetermined.Protein
expression,immunohistochemicalstainingwereevaluatedinharvestedtumortissues.
Results: Noscapine inhibited growth of MDA-MB-231 and MDA-MB-468 cells with the IC values of 36.1663.76 and
50
42.764.3mMrespectively.TheCIvalues(,0.59)weresuggestiveofstrongsynergisticinteractionbetweenNoscapineand
Doxorubicinandcombinationtreatmentshowedsignificantincreaseinapoptoticcells.Noscapineshoweddosedependent
reduction in the tumor volumes at a dose of 150–550mg/kg/day compared to controls. Noscapine (300mg/kg),
Doxorubicin(1.5mg/kg)andcombinationtreatmentreducedtumorvolumeby39.465.8,34.265.7and82.964.5percent
respectivelyandshoweddecreasedexpressionofNF-KBpathwayproteins,VEGF,cellsurvival,andincreasedexpressionof
apoptoticandgrowthinhibitoryproteinscomparedtosingle-agenttreatmentandcontrolgroups.
Conclusions:NoscapinepotentiatedtheanticanceractivityofDoxorubicininasynergisticmanneragainstTNBCtumorsvia
inactivationofNF-KBandanti-angiogenicpathwayswhilestimulatingapoptosis.Thesefindingssuggestpotentialbenefit
foruseoforalNoscapineandDoxorubicincombinationtherapyfortreatmentofmoreaggressiveTNBC.
Citation: Chougule MB, Patel AR, Jackson T, Singh M (2011) Antitumor Activity of Noscapine in Combin
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