Peptide-Mediated Transduction of Proteins and Nucleic Acids to Prevent and Treat Experimental Prostate Cancer.

摘要

The goal of this project is to prevent bone metastasis in early experimental prostate cancer using protein transduction: the ability of small peptides to facilitate the entry of large biologically active fusion protein cargos into cells. The hypothesis to be tested is that protein transduction can deliver therapeutic proteins to skeletal tissues and bone marrow in such a manner that they may facilitate the apoptotic, or programmed cell death of cancerous cells. Dr. Whalen and colleagues have previously shown that protein transduction can allow many proteins into organs previously unaccessible to other delivery methods (drugs, viral vectors etc). Her research team has constructed unique protein-transduction domains (PTD5 and Lys8) which facilitate the entry and activity of the tumor suppressive p53 or pro-apoptotic peptide Smac34 into prostate cancer cell lines. Unfortunately, these fusion peptides exhibited no or weak activities in prostate cancer cells. As an alternative, Dr. Whalen s team tried to explore the feasibility of adapting liposome mediated antisense gene therapy targeting EGFR for prostate cancer treatment, using murine models with xenografts of PC3 prostate cancer cells. Antisense gene therapy may prove to be useful for prostate cancer treatment.