Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostatic Carcinoma Cells

摘要

G-rich oligonucleotides (GROs) are a novel class of non-antisense nucleic acids that exhibit potent antiproliferative effects against malignant cells, including prostate cancer cells. The mechanism of GRO antiproliferative activity depends on their binding to nucleolin protein. Because they work by a novel mechanism (different from antisense oligonucleotides or traditional chemotherapy agents) and are expected to have few side effects, they have promise as new therapeutic agents for the treatment of prostate cancer. The major aims of this study were to test the efficacy of GROs in inhibiting the growth and metastasis of prostate cancer in rodent models, to investigate the mechanism of GROs, and to develop structural models of nucleolin (the primary target of GROs) for the development of new inhibitors. The formulation and delivery of GROs have been optimized in vitro and in vivo. In addition, GROs have demonstrated impressive inhibitory effects against an aggressive hormone- independent tumor (DU145) in mice. In summary, the results strongly support the potential of GROs as novel therapeutic agents for prostate cancer.