Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer

C Wilson, P Scullin, Jenny Worthington, A Seaton, P Maxwell, D O'Rourke, PG Johnston, Stephanie McKeown, RH Wilson, JM O'Sullivan, DJJ Waugh

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    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.
    LanguageEnglish
    Pages2054-2064
    JournalBRITISH JOURNAL OF CANCER
    Volume99
    Issue number12
    DOIs
    Publication statusPublished - Dec 2008

    Fingerprint

    docetaxel
    Castration
    Dexamethasone
    Prostatic Neoplasms
    NF-kappa B
    Interleukin-8
    Bone Marrow Cells
    Endothelial Cells
    Neoplasms
    Transcription Factor AP-1
    Residual Neoplasm
    Vascular Endothelial Growth Factor A
    Blood Vessels

    Cite this

    Wilson, C., Scullin, P., Worthington, J., Seaton, A., Maxwell, P., O'Rourke, D., ... Waugh, DJJ. (2008). Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer. BRITISH JOURNAL OF CANCER, 99(12), 2054-2064. https://doi.org/10.1038/sj.bjc.6604804
    Wilson, C ; Scullin, P ; Worthington, Jenny ; Seaton, A ; Maxwell, P ; O'Rourke, D ; Johnston, PG ; McKeown, Stephanie ; Wilson, RH ; O'Sullivan, JM ; Waugh, DJJ. / Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer. In: BRITISH JOURNAL OF CANCER. 2008 ; Vol. 99, No. 12. pp. 2054-2064.
    @article{0a44934b0c754f0a8f4210ef686f4ed3,
    title = "Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer",
    abstract = "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.",
    author = "C Wilson and P Scullin and Jenny Worthington and A Seaton and P Maxwell and D O'Rourke and PG Johnston and Stephanie McKeown and RH Wilson and JM O'Sullivan and DJJ Waugh",
    year = "2008",
    month = "12",
    doi = "10.1038/sj.bjc.6604804",
    language = "English",
    volume = "99",
    pages = "2054--2064",
    journal = "BRITISH JOURNAL OF CANCER",
    issn = "0007-0920",
    number = "12",

    }

    Wilson, C, Scullin, P, Worthington, J, Seaton, A, Maxwell, P, O'Rourke, D, Johnston, PG, McKeown, S, Wilson, RH, O'Sullivan, JM & Waugh, DJJ 2008, 'Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer', BRITISH JOURNAL OF CANCER, vol. 99, no. 12, pp. 2054-2064. https://doi.org/10.1038/sj.bjc.6604804

    Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer. / Wilson, C; Scullin, P; Worthington, Jenny; Seaton, A; Maxwell, P; O'Rourke, D; Johnston, PG; McKeown, Stephanie; Wilson, RH; O'Sullivan, JM; Waugh, DJJ.

    In: BRITISH JOURNAL OF CANCER, Vol. 99, No. 12, 12.2008, p. 2054-2064.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer

    AU - Wilson, C

    AU - Scullin, P

    AU - Worthington, Jenny

    AU - Seaton, A

    AU - Maxwell, P

    AU - O'Rourke, D

    AU - Johnston, PG

    AU - McKeown, Stephanie

    AU - Wilson, RH

    AU - O'Sullivan, JM

    AU - Waugh, DJJ

    PY - 2008/12

    Y1 - 2008/12

    N2 - 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.

    AB - 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.

    U2 - 10.1038/sj.bjc.6604804

    DO - 10.1038/sj.bjc.6604804

    M3 - Article

    VL - 99

    SP - 2054

    EP - 2064

    JO - BRITISH JOURNAL OF CANCER

    T2 - BRITISH JOURNAL OF CANCER

    JF - BRITISH JOURNAL OF CANCER

    SN - 0007-0920

    IS - 12

    ER -