Prostate cancer incidence has been steadily increasing and is the second leading cause of death from cancer in American men. Although androgen ablation therapy is initially useful in controlling tumor progression, prostate tumors eventually become unresponsive to this therapy. The lack of effective treatments for advanced prostate cancer has spurred research toward the development of novel therapeutic methods to treat the disease. Therefore, much effort is needed to understand the mechanisms involved in the development and progression of prostate cancer and to develop new strategies for its prevention and treatment.

There is ample evidence that there is a decreased risk of prostate cancer in people who regularly take aspirin or other anti-inflammatory drugs to inhibit Cyclooxygenase (COX) activity. Epidemiological data also suggested that vitamin D may have a beneficial effect against prostate cancer. In our findings, treatment of prostate cancer cells with COX-2 inhibitor NS-398 induces vitamin D receptor expression, which results in increasing the vitamin D sensitivity of such cells. In return, treatment of prostate cancer cells with vitamin D results in a reduction of COX-2 mRNA expression. This interplay between vitamin D and the COX-2 inhibitor provides a strong reason to combine these two compounds in the treatment of prostate cancer. In this proposal, we will examine the effects of combining vitamin D and COX-2 inhibitor in prostate cancer development and progression. Both cell lines and animal models will be used in our study to prove our findings. These efforts may then be translated almost immediately into clinical trials and provide the basis for a new therapeutic paradigm for this disease. Ultimately, this research may help extend the lives of the nearly 30,000 American men who succumb to prostate cancer annually.