Experimental therapy of prostate cancer with an immunomodulatory oligonucleotide: Effects on tumor growth, apoptosis, proliferation, and potentiation of chemotherapy

BACKGROUND. The present study was designed to demonstrate the therapeutic efficacy of a novel immunomodulatory oligonucleotide (IMO) for prostate cancer. METHODS. We evaluated the effects of the IMO in xenograft (PC-3) and syngeneic (TRAMP C1) models of prostate cancer, and in prostate cancer cells. The IMO was also evaluated in combination with chemotherapy, and the in vitro expression of TLR9 was examined. RESULTS. The IMO had significant anti-tumor activity in both prostate cancer models and almost complete tumor regression was observed when the IMO was combined with taxotere or gemcitabine. TLR9 mRNA and protein were both expressed in prostate cancer cells. The IMO also induced apoptosis and decreased proliferation and survival of PC-3 cells in vitro in the presence of Lipofectin. CONCLUSIONS. The IMO inhibits prostate cancer growth in vivo and in vitro, and potentiates the effects of conventional chemotherapeutic agents. This is the first report of TLR9 expression in prostate cancer cells.