Sensitization of PARP inhibitor through ionizing radiation induced BRCA1 nuclear export
JIANG Ju-hong
GU Ying-ying
LIU Jing
FU Xin-ge
Abstract：Objective To investigate the sensitization of PARP inhibitor through ionizing radiation ( IR) induced BRCA1 nuclear export, and the consequent defiency in DNA double strand break -repair function.Methods The loca-tion of BRCA1 in nuclear or/and cytoplasmic compartments was assessed by subcellular fractionation in MCF 7 cells after IR.The formation of γ-H2AX and Rad51 foci were detected by immunofluorescence staining .After labeled with Annexin V-FITC, apoptotic cells were analyzed by flow cytometry .In vivo anti-tumor activity was evaluated in MCF 7 xenograf-ted SCID mice.Results Nuclear BRCA1 of IR in treated cells were 41% that of mock irradiated cells .Cytoplasmic BRCA1 of IR in treated cells were 2.14 folds compare to that of mock irradiated cells .ABT-888 induced 7%and 30%Rad51 positive cell in IR treated or mock irradiated cells , respectively .Combined treatment of IR and ABT -888 induced 19%apoptosis cells, significantly higher than IR and ABT -888 alone.The combination of IR with ABT -888 in MCF7 xenograft model resulted in a superior therapeutic response compared to the single -agent alone .Conclusion Ionizing ra-diation can induced BRCA 1 nuclear export and sensitize PARP inhibitor .
Keywords：ionizing radiationBRCA1 nuclear exportPARP inhibitorhomologous recombination
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 2901-2906 )