Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K, Department of Urology, Tokyo Medical and Dental University, Yushima, Tokyo, Japan

Jennifer J. Westendorf, Luke Hoeppner

Research output: Contribution to journalShort surveypeer-review

1 Scopus citations

Abstract

Purpose: Glucocorticoids, such as prednisone, hydrocortisone, and dexamethasone, are known to produce some clinical benefit for patients with hormone-refractory prostate cancer (HRPC). However, the underlying mechanisms by which glucocorticoids affect HRPC growth are not well established as yet. Here, we hypothesize that the therapeutic effect of glucocorticoids on HRPC can be attributed to a direct inhibition of angiogenesis through the glucocorticoid receptor by down-regulating two major angiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). Experimental Design: The effects of dexamethasone on VEGF and IL-8 expression and cell proliferation were examined using DU145, which expresses glucocorticoid receptor. The effects of dexamethasone on DU145 xenografts were determined by analyzing VEGF and IL-8 gene expression, microvessel density, and tumor volume. Results: Dexamethasone significantly down-regulated VEGF and IL-8 gene expression by 50% (P < 0.001) and 89% (P < 0.001), respectively, and decreased VEGF and IL-8 protein production by 55% (P < 0.001) and 74% (P < 0.001), respectively, under normoxic condition. Similarly, hydrocortisone down-regulated VEGF and IL-8 gene expression. The effects of dexamethasone were completely reversed by the glucocorticoid receptor antagonist RU486. Even under hypoxia-like conditions, dexamethasone inhibited VEGF and IL-8 expression. In DU145 xenografts, dexamethasone significantly decreased tumor volume and microvessel density and down-regulated VEGF and IL-8 gene expression, whereas dexamethasone did not affect the in vitro proliferation of the cells. Conclusion: Glucocorticoids suppressed androgen-independent prostate cancer growth possibly due to the inhibition of tumor-associated angiogenesis by decreasing VEGF and IL-8 production directly through glucocorticoid receptor in vivo.

Original languageEnglish (US)
Pages (from-to)181-182
Number of pages2
JournalUrologic Oncology: Seminars and Original Investigations
Volume25
Issue number2
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint

Dive into the research topics of 'Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K, Department of Urology, Tokyo Medical and Dental University, Yushima, Tokyo, Japan'. Together they form a unique fingerprint.

Cite this