Open AccessDigoxin Inhibits Blood Vessel Density and HIF‐1a Expression in Castration‐Resistant C4‐2 Xenograft Prostate Tumors
Author(s) -
Gayed Bishoy A.,
O’Malley Katherine J.,
Pilch Jan,
Wang Zhou
Publication year - 2012
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2011.00376.x
Subject(s) - prostate cancer , digoxin , cd31 , medicine , prostate , castration , immunostaining , endocrinology , immunohistochemistry , cancer research , cancer , hormone , heart failure
Purpose: Recent studies suggest a potential application for digoxin in the prevention and/or treatment of prostate cancer. However, the effect of digoxin on androgen receptor (AR)‐positive prostate tumor in vivo is not clear. This study is designed to determine if digoxin can inhibit AR‐positive xenograft prostate tumors. Materials and Methods: Athymic male nude mice were utilized to establish subcutaneous C4‐2 castration‐resistant prostate tumors. The animals were castrated and then treated with daily intraperitoneal (i.p.) injection of digoxin at 2mg/kg along with vehicle controls for 7 consecutive days. Tumor growth was determined by measuring tumor volume changes, blood vessel density by immunostaining of CD31, and cell proliferation by BrdU labeling. The expression of HIF‐1a in C4‐2 tumors was measured by Western blot and real‐time RT‐PCR. Results: Digoxin inhibited blood vessel density about fourfold and down‐regulated HIF‐1a expression at both mRNA and protein levels. However, digoxin did not inhibit C4‐2 tumor growth. Conclusions: Digoxin is a potent inhibitor of HIF‐1a signaling pathway and blood vessel formation in C4‐2 castration‐resistant prostate tumors. Clin Trans Sci 2012; Volume #: 1–4