Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Clin Transl Sci. 2012 Feb;5(1):39-42. doi: 10.1111/j.1752-8062.2011.00376.x. Epub 2012 Feb 23.
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.
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 2 mg/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-1α in C4-2 tumors was measured by Western blot and real-time RT-PCR.
Digoxin inhibited blood vessel density about fourfold and down-regulated HIF-1α expression at both mRNA and protein levels. However, digoxin did not inhibit C4-2 tumor growth.
Digoxin is a potent inhibitor of HIF-1α signaling pathway and blood vessel formation in C4-2 castration-resistant prostate tumors.
最近的研究表明，地高辛在预防和/或治疗前列腺癌方面可能有一定的应用前景。然而，地高辛对体内雄激素受体（AR）阳性前列腺肿瘤的影响尚不清楚。本研究旨在确定地高辛是否能抑制 AR 阳性异种移植前列腺肿瘤。
利用无胸腺雄性裸鼠建立皮下 C4-2 去势抵抗性前列腺肿瘤模型。动物去势后，每天腹腔内（i.p.）注射 2mg/kg 的地高辛，并与载体对照一起连续治疗 7 天。通过测量肿瘤体积变化、CD31 免疫染色测定血管密度以及 BrdU 标记测定细胞增殖来确定肿瘤生长情况。通过 Western blot 和实时 RT-PCR 测定 C4-2 肿瘤中的 HIF-1α表达。
地高辛使血管密度降低了约 4 倍，并在 mRNA 和蛋白水平下调了 HIF-1α 的表达。然而，地高辛并没有抑制 C4-2 肿瘤的生长。
地高辛是 C4-2 去势抵抗性前列腺肿瘤中 HIF-1α信号通路和血管形成的有效抑制剂。
