Human telomerase reverse transcriptase antisense treatment downregulates the viability of prostate cancer cells in vitro

Telomerase, a ribonucleoprotein complex is activated in the vast majority o f human malignancies, including prostate cancer. Its inhibition is a putati ve way to affect cancer proliferation and might be used in the therapy of t umors. We analysed the influence of antisense phosphorothioate oligonucleot ides (PTO) against the reverse transcriptase subunit of telomerase on prost ate cancer cell viability, telomerase activity and telomere length. DU145 p rostate cancer cells were cultivated in PTO containing medium. The PTO-inco rporation was confirmed by confocal laser scanning microscopy. Cell viabili ty was measured by a WST-1 tetrazolium assay. After 15 days of antisense PT O treatment, a significant inhibition of cell viability occurred. Telomeras e activity was determined by a telomeric repeat amplification protocol (TRA P) assay and telomere length by Southern blot analysis. Since the long-term telomerase antisense treatment reduces the viability of prostate cancer ce lls significantly, this antisense approach could be a new therapeutic strat egy to treat patients with advanced prostate cancer.