Wilson, C, Scullin, P, Worthington, Jenny, Seaton, A, Maxwell, P, O'Rourke, D, Johnston, PG, McKeown, Stephanie, Wilson, RH, O'Sullivan, JM and Waugh, DJJ (2008) Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer. BRITISH JOURNAL OF CANCER, 99 (12). pp. 2054-2064. [Journal article]
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We sought to characterise whether dexamethasone (DEX) may enhance tumour response to docetaxel in in vitro and in vivo models of metastatic prostate cancer (CaP). In vitro experiments conducted on PC3 and human bone marrow endothelial cells (hBMECs) determined that administration of DEX (10 nM) reduced constitutive nuclear factor-kappa B (NF-kappa B) activity, decreasing interleukin (IL)-8, CXCL1 and VEGF gene expression in PC3 cells. Dexamethasone also attenuated docetaxel-induced NF-kappa B and activator protein-1 transcription and reduced docetaxel-promoted expression/secretion of IL-8 and CXCL1 in PC3 and hBMECs. Although DEX failed to enhance docetaxel cytotoxicity on PC3 cells, DEX potentiated the antiangiogenic activity of docetaxel in vitro, further reducing vessel area and vessel length in developing endothelial tubes (P < 0.05). Docetaxel had a potent antiangiogenic activity in the dorsal skin flap-implanted PC3 tumours in vivo. Small blood vessel formation was further suppressed in tumours co-treated with docetaxel and DEX, substantiated by an increased average vessel diameter and segment length and a decreased number of branch points in the residual tumour vasculature (P < 0.001). Our data show that DEX potentiates the antiangiogenic activity of docetaxel, suggesting a putative mechanism for the palliative and survival benefits of these agents in metastatic CaP.
|Item Type:||Journal article|
|Faculties and Schools:||Faculty of Life and Health Sciences|
Faculty of Life and Health Sciences > School of Biomedical Sciences
|Research Institutes and Groups:||Biomedical Sciences Research Institute|
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Pharmaceutical Science and Practice
Biomedical Sciences Research Institute > Molecular Medicine > Transcriptional Regulation & Epigenetics
|Deposited By:||Professor Stephanie McKeown|
|Deposited On:||05 Jan 2010 16:03|
|Last Modified:||23 Jun 2011 15:59|
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