To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination With Vitamin D, in Vitro and in Vivo.

摘要

The incidence of prostate cancer has increased rapidly and much effort is needed towards understanding the mechanisms involved in development and progression of prostate cancer and developing new strategies for its prevention and treatment. Recent studies have suggested that nonsteroidal anti- inflammatory drugs (NSAIDs), such as COX-2 inhibitor act as chemopreventative agents. Prostate Tissue Microarray analyses found that COX-2 expression in prostate cancer was correlated with cancer progression. Treatment of prostate cancer cells with a selective COX-2 inhibitor, NS-398, induces VDR expression, and thus might result in increasing the vitamin D sensitivity. In return, treatment of prostate cancer cells with 1,25- VD results in reduction of COX-2 expression. Based on the bi-directional regulation involving vitamin D and the COX-2 inhibitor, we hypothesize that combining vitamin D and a COX-2 inhibitor in the treatment of prostate cancer will be beneficial to the treatment of prostate cancer. Four aims are proposed. 1: Evaluation of the molecular mechanism of COX-2 inhibitor NS- 398 action on the growth of prostate cancer cells. 2: Evaluation of the effects of I ,25-VD and its analogs in combination with COX-2 inhibitor on progression of prostate cancer cells. 3: Evaluation of the underlying mechanism of the bi-directional regulatory pathways between the COX-2 inhibitor NS-398 and vitamin D. 4:Evaluation of the effects of COX-2 inhibitor, administered in combination with vitamin D compounds, on prostate cancer progression and invasion in vivo.