Shetty Aditya, Dasari Subramanyam, Banerjee Souresh, Gheewala Taher, Zheng Guoxing, Chen Aoshuang, Kajdacsy-Balla Andre, Bosland Maarten C, Munirathinam Gnanasekar
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Department of Pathology, University of Illinois at Chicago, Chicago, IL.
Urol Oncol. 2016 Nov;34(11):483.e1-483.e8. doi: 10.1016/j.urolonc.2016.05.027. Epub 2016 Sep 28.
Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival-related protein as ectopic overexpression of HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX. Western blot analysis also showed that HDGF overexpression modulated the activity of phospho-AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k, showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF overexpressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K. Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer.
肝癌衍生生长因子（HDGF）是一种肝素结合生长因子，此前已证实在多种癌症中表达。HDGF过表达此前也与多种癌症的不良预后相关。然而，HDGF在前列腺癌中的意义尚未得到研究。在此，我们表明HDGF在雄激素敏感的LNCaP细胞以及雄激素不敏感的DU145、22RV1和PC - 3细胞中均过表达。强制过表达增强了RWPE - 1细胞的活力，而HDGF敲低则降低了人前列腺癌细胞的增殖。我们还表明，HDGF可能作为一种与生存相关的蛋白，因为在RWPE细胞中异位过表达HDGF会上调抗凋亡蛋白细胞周期蛋白E和BCL - 2的表达，同时下调促凋亡蛋白BAX。蛋白质印迹分析还表明，HDGF过表达调节了磷酸化AKT以及NF - kB的活性，这些结果与体外迁移和侵袭试验相关。接下来，我们用HDGF单克隆抗体和维生素K评估了HDGF抑制的治疗潜力，结果显示在用HDGF单克隆抗体和维生素K处理的HDGF过表达的RWPE细胞中，细胞增殖减少以及NF - kB表达受到抑制。总体而言，我们的结果表明HDGF是前列腺癌发生过程中的一种相关蛋白，并且可能作为前列腺癌的一个潜在治疗靶点。
