Digoxin inhibits blood vessel density and HIF-1a expression in castration-resistant C4-2 xenograft prostate tumors

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Emerging research indicates potential roles for digoxin in prostate cancer management.
• The in vivo efficacy of digoxin against androgen receptor (AR)-positive prostate tumors remains largely uninvestigated.

Purpose of the Study:

• To evaluate the inhibitory effect of digoxin on AR-positive xenograft prostate tumors.
• To determine if digoxin can impede the growth of castration-resistant prostate tumors.

Main Methods:

• Subcutaneous C-2 castration-resistant prostate tumors were established in athymic male nude mice.
• Mice received daily intraperitoneal injections of digoxin (2 mg/kg) or vehicle control for seven days post-castration.
• Tumor growth, blood vessel density (CD31 staining), cell proliferation (BrdU labeling), and HIF-1α expression (Western blot, RT-PCR) were assessed.

Main Results:

• Digoxin treatment led to a fourfold reduction in tumor blood vessel density.
• Digoxin significantly down-regulated HIF-1α at both mRNA and protein levels.
• Despite anti-angiogenic effects, digoxin did not inhibit overall C-2 tumor growth.

Conclusions:

• Digoxin demonstrates potent inhibition of the HIF-1α signaling pathway.
• Digoxin effectively suppresses blood vessel formation within C-2 castration-resistant prostate tumors.