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Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer
- Source :
- British Journal of Cancer
- Publication Year :
- 2008
- Publisher :
- Springer Science and Business Media LLC, 2008.
-
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-kappaB (NF-kappaB) activity, decreasing interleukin (IL)-8, CXCL1 and VEGF gene expression in PC3 cells. Dexamethasone also attenuated docetaxel-induced NF-kappaB 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 (P0.05). 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 (P0.001). 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.
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Angiogenesis
dexamethasone
Angiogenesis Inhibitors
Docetaxel
urologic and male genital diseases
angiogenesis
Mice
Prostate cancer
In vivo
Cell Line, Tumor
Internal medicine
medicine
Animals
Humans
Interleukin 8
Molecular Diagnostics
neoplasms
Dexamethasone
business.industry
Interleukin-8
NF-kappa B
Endothelial Cells
Prostatic Neoplasms
Interleukin
prostate cancer
medicine.disease
Xenograft Model Antitumor Assays
Transcription Factor AP-1
CXCL1
Endocrinology
Oncology
Cancer research
Taxoids
business
Orchiectomy
medicine.drug
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....cb822af9fd955721a798478681eb7786