Inhibition of LNCaP prostate tumor growth in vivo by an antisense oligonucleotide directed against the human androgen receptor

摘要: We have shown recently that a 15-mer phosphorothioate oligodeoxynucleotide (ODNas750/15) hybridizes to the (CAG)n polyglutamine region of mRNA encoding human androgen receptor (AR) inhibits expression AR in LNCaP prostate cancer cells vitro. This downregulation was accompanied by significant cell growth inhibition and reduced PSA secretion. In present study we investigated effects this antisense ODN on tumor vivo using mouse xenograft model. Via subcutaneously implanted diffusion pumps, either ODNas750/15 or scrambled control sequence ODNsr750/15 continuously administered into tumor-bearing male nude mice for 7 weeks. Compared with untreated animals, treatment resulted inhibition. Retardation also castrated mice, whereas did not exert any effects. No side such as loss body weight were observed at time treatment. well tolerated and, contrast castration, induce shrinkage prostates. Both levels serum correlated size. However, failed demonstrate correlation between retardation Ki-67 antigen number apoptotic cells, respectively. Testing antisense-treated revealed other proteins contain shorter stretches HDAC2, TFIID, c-jun affected. The demonstrates causes These results further point out important role tumors support testing cancer.