Fig. 7

SAHA and veliparibsynergistically destroyed the protein stability of UHRF1 and BRCA1. a The mRNA expression of UHRF1 and BRCA1 showed a high positive correlation in 495 PCa samples from TCGA data (R = 0.6864). b Co-treatment with SAHA and veliparib decreased co-localization of UHRF1 and BRCA1 proteins. LNCaP cells were treated with SAHA (1uM) and veliparib (20uM) for 48 h, and then reacted with UHRF1 and green fluorescent secondary antibodies or BRCA1 and red fluorescent secondary antibodies. The nuclei were labeled with DAPI. The co-localization of UHRF1 and BRCA1 was observed with a fluorescence microscopy. c Co-treatment with SAHA and veliparib decreased the protein interaction of BRCA1 and UHRF1. UHRF1 and BRCA1 were up-regulated in HEK-293 cells by transient transfection. The HEK-293 and Hela cells were treated with or without SAHA and veliparib, UHRF1 protein was co-immunoprecipitated (co-IP), and BRCA1 protein was identified in the protein complex by western blot. d BRCA1 protein levels were tested when UHRF1 was depleted with siRNA in VCaP and HEK-293 cells. e BRCA1 protein levels were tested when LNCaP and VCaP cells were co-treated with SAHA and veliparib with or without the elevation of UHRF1 level. f DU145 tumor xenografts were induced in nude mice, and then were treated with vehicle or drugs for continuous 3 weeks. The volumes of xenografts were monitored (**P < 0.01,*P < 0.05, compared to other three group). g The body weight of nude mice was monitored during the entire treatment. h and i The tumors were isolated at the endpoint of experiment, and the size and weight of tumors were compared