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Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin‐like growth factor receptor
Author(s) -
Hellawell G.O.,
Ferguson D.J.P.,
Brewster S.F.,
Macaulay V.M.
Publication year - 2003
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2003.04061.x
Subject(s) - prostate cancer , insulin like growth factor receptor , insulin like growth factor , cancer research , receptor , insulin receptor , growth factor , cancer , insulin , medicine , insulin resistance
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.