Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin‐like growth factor receptor
Open Access
- 4 February 2003
- journal article
- research article
- Published by Wiley in BJU International
- Vol. 91 (3) , 271-277
- https://doi.org/10.1046/j.1464-410x.2003.04061.x
Abstract
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.Keywords
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