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OBJECTIVE: To assess the effect of the downregulation of type 1 insulin-like growth factor receptor (IGF1R) on the chemosensitivity of prostate cancer cells. IGF1R is overexpressed by prostate cancer compared with benign prostatic epithelium and IGF1R expression commonly persists in androgen-independent metastatic disease at levels comparable to those in the primary. MATERIALS AND METHODS: Human androgen-independent DU145 prostate cancer cells were transfected with IGF1R antisense oligonucleotides or antisense RNA. Transfected cultures were treated with cisplatin, mitoxantrone, paclitaxel or vehicle control, and survival measured using a clonogenic assay. RESULTS: Both antisense strategies suppressed IGF1R protein levels to 30-50% of those in control cultures. This was associated with 1.5-2-fold enhancement of sensitivity to cisplatin, mitoxantrone and paclitaxel, and an increase in cisplatin-induced apoptosis. CONCLUSION: This approach has potential for development as a clinical treatment for advanced prostate cancer and other chemoresistant tumours.

Type

Journal article

Journal

BJU Int

Publication Date

02/2003

Volume

91

Pages

271 - 277

Keywords

Antineoplastic Agents, Apoptosis, Cisplatin, Down-Regulation, Humans, Male, Mitoxantrone, Oligonucleotides, Antisense, Paclitaxel, Prostatic Neoplasms, Receptor, IGF Type 1, Transfection, Tumor Cells, Cultured, Tumor Stem Cell Assay