To Investigate the Therapeutic Effects of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination with Vitamin D, in Vitro and in Vivo
Abstract
The incidence of prostate cancer has increased and effort is needed towards understanding mechanisms involved in development/progression of prostate cancer and developing new strategies for prevention/treatment. Studies suggested nonsteroidal anti-inflammatory drugs, such as COX-2 inhibitor, act as chemopreventative agents and found COX-2 expression in prostate cancer correlated with cancer progression. Treatment of prostate cancer cells with COX-2 inhibitor, NS-398, induces VDR expression, and might increase vitamin D sensitivity. Treatment of prostate cancer cells with 1,25-VD results in reduced COX- 2 expression. Based on the bi-directional regulation of vitamin D and COX-2 inhibitor, we hypothesize that combining vitamin D and COX-2 inhibitor in treatment of prostate cancer will be beneficial. Over the past year, we identified the molecular mechanism by which vitamin D inhibits prostate cancer angiogenesis through IL-8, finding a strong correlation of IL-8 expression with prostate cancer disease progression, therefore, inhibition of IL-8 by vitamin D supports the chemotherapeutic effects of vitamin D in preventing prostate cancer progression. The clinical use of COX-2 inhibitors has recently become controversial due to cardiovascular complications associated with the use of COX-2 inhibitor for prolonged periods of time. Therefore in addition to combination with COX-2 inhibitor, vitamin D-based combination therapy was developed. Docetaxel is the only treatment shown to improve overall survival in hormonal refractory prostate cancer patients; however the survival benefit is modest. Treatment with docetaxel in combination with vitamin D has shown promising results in prostate specific antigen response, time to progression and survival in HRPC patients. Detailed mechanism of this combination therapy was studied to provide a further therapeutic design.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2007
- Accession Number
- ADA472121
Entities
People
- Yi-fen Lee
Organizations
- University of Rochester