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.
Rayburn
Elizabeth R
ER
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, 35294-0019, USA.
Wang
Wei
W
Zhang
Zhuo
Z
Li
Mao
M
Zhang
Ruiwen
R
Wang
Hui
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000276:immunology / Q000627:therapeutic use*; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
D007155:Immunologic Factors; D009841:Oligonucleotides; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D043823:Taxoids; D051217:Toll-Like Receptor 9; D003841:Deoxycytidine; D000077143:Docetaxel; C020888:1,2-dielaidoylphosphatidylethanolamine; D000093542:Gemcitabine