Molecular Mechanisms of Essential Fatty Acids and Metabolites in Regulation of Prostate Cancer Cells

摘要

Prostate cancer is a heterogeneous disease for which the only effective treatments for organ-confined cancer at this time include radical surgery, radiation or androgen ablation/hormonal therapy. But advanced prostate cancer is almost no cure. Effective ways to prevent and/or treat advanced prostate cancer are needed. Our recent work has shown that a terminal metabolite, 15-deoxy-delta l2, 14-prostaglandin J2 (15d-PGJ2), of some essential polyunsaturated fatty acids can induce cell death of human and mouse prostate cancer cells and overexpression of heat shock protein 70 (Hsp70). Our preliminary results also demonstrated that Hsp70 purified from 15d-PGJ2 treated prostate cancer cells can induce prostate cancer specific immunity which can highly effectively prevent cancer growth. Tumor-associated peptides in purified Hsp70 from cancer cells are critical for induction of cancer-specific immunity. We hypothesize that heat shock protein from 15d-PGJ2 treated prostate cancer cells can generate higher anti-tumor immunity than that from untreated cancer cells and that 15d-PGJ2 may be a useful chemotherapeutic and immunotherapeutic agent for prostate cancer. Because a fall immune competent host is required to evaluate and validate this proposed study before it can be tested in humans, TRAMP C2 cells and syngeneic male mice will be used for this proposal. This proposal will establish whether 15d-PGJ2 treatment will exhibit both chemotherapeutic and immunotherapeutic benefits for combating prostate cancer in animal models. If these goals can be accomplished, initial clinical trials would be appropriate to pursue in the near future.