Telomerase Inhibition and Chemosensitization of Prostate Cancer Cells

摘要

Telomerase is expressed in most types of tumor cells but not in most somatic cells suggesting that telomerase inhibitors may be a powerful new approach to cancer chemotherapy. Here we explore this hypothesis by treating cultured human tumor cells with a 2'-O-methoxyethyl (MOE) oligonucleotide that bids the telomerase RNA template and acts as a potent inhibitor. Treatment of DU145 (p53-) and LNCaP (p53+) cells causes telomeres to shorten and causes cell proliferation to stop. Decreased cell proliferation is not observed immediately, but occurs after several weeks and is accompanied by telomere shortening and increased chromosomal abnormalities. The combination of telomerase inhibitors with other doxyrubicin, etoposide, paclitaxel does not increase antiproliferative effects, but co-administered of telomerase inhibitor and cisplatin or carboplatin does cause a significant synergistic reduction in cell proliferation. These results demonstrate that MOE oligomers directed against the template region of telomerase are potent antiproliferative agents.