Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models
Abstract
One critically important problem in prostate cancer research is to find new approaches to slow down the transition of prostate cancer from an androgen-dependent state to a lethal androgen-refractory state. Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells. However, the advantage of inducing differentiation of prostate cancer cells by intermittent recovery of androgens is compromised by the disadvantage of androgenic induction of prostate cancer cell proliferation. The biologically most active androgen is dihydrotestosterone (DHT) which is converted from testosterone (T) by Sa-reductase. Our recent studies showed that T is more potent than DHT in enhancing differentiation but weaker in stimulating proliferation, which led to our hypothesis that intermittent androgen suppression (IAS) can be enhanced by finasteride, an inhibitor of T to DHT conversion. We have worked out conditions to deliver T and finasteride over a long time period in nude mice, which allowed us to test our hypothesis. Our experiments recently showed that finasteride administration during IAS significantly slowed the growth of LNCaP tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423671
Entities
People
- Zhou Wang
Organizations
- Northwestern University