Cancer gene therapy, 2000-07, Vol.7 (7), p.997-1007
2000
Details
- Autor(en) / Beteiligte
- Titel
- Inhibition of LncaP prostate cancer cells by means of androgen receptor antisense oligonucleotides
- Ist Teil von
- Cancer gene therapy, 2000-07, Vol.7 (7), p.997-1007
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2000
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Currently available methods for treatment of human prostatic carcinoma aim to inactivate the androgen receptor (AR) by androgen deprivation or blockade with anti-androgens. Failure of endocrine therapy and tumor progression is characterized by androgen-independent growth despite high levels of AR expression in metastatic disease. We inhibited AR expression in LNCaP prostate tumor cells by using antisense AR oligodeoxynucleotides (ODNs) and explored whether antisense AR treatment would be conceivable as a therapy for advanced prostate cancer. Among the various AR antisense ODNs tested, a 15-base ODN targeting the CAG repeats encoding the poly-glutamine region of the AR (as750/15) was found to be most effective. Treatment of LNCaP cells with as750/15 reduced AR expression to approximately 2% within 24 hours compared with mock-treated controls. AR down-regulation resulted in significant cell growth inhibition, strongly reduced secretion of the androgen-regulated prostate-specific antigen, reduction of epidermal growth factor receptor expression, and an increase in apoptotic cells. Mis-sense and mismatched control ODNs had no or only slight effects. Antisense inhibition was also very efficient in LNCaP-abl cells, a subline established after long-term androgen ablation of LNCaP cells, resulting in inhibition of AR expression and cell proliferation that was similar to that seen for parental LNCaP cells. This study shows that inhibition of AR expression by antisense AR ODNs may be a promising new approach for treatment of advanced human prostate cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0929-1903eISSN: 1476-5500DOI: 10.1038/sj.cgt.7700202Titel-ID: cdi_proquest_miscellaneous_71266080
- Format
- –
- Schlagworte
- Androgen receptors, Androgens, Antisense oligonucleotides, Apoptosis, Cell Division, Cell growth, Cell proliferation, DNA Primers - chemistry, Down-Regulation, Endocrine therapy, Enzyme-Linked Immunosorbent Assay, Epidermal growth factor, Genetic Therapy, Glutamine, Growth inhibition, Humans, Immunoblotting, Male, Metastases, Oligodeoxyribonucleotides, Antisense - therapeutic use, Oligonucleotides, Polyglutamine, Prostate cancer, Prostate-specific antigen, Prostate-Specific Antigen - analysis, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - pathology, Prostatic Neoplasms - therapy, Receptor, Epidermal Growth Factor - metabolism, Receptors, Androgen - genetics, Receptors, Androgen - metabolism, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - analysis, Time Factors, Trinucleotide repeats, Tumor cells, Tumor Cells, Cultured