Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor

被引:54
作者
Hellawell, GO
Ferguson, DJP
Brewster, SF
Macaulay, VM [1 ]
机构
[1] John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Labs, Oxford OX3 9DS, England
[2] John Radcliffe Hosp, Nuffield Dept Pathol, Oxford OX3 9DS, England
[3] Churchill Hosp, Dept Urol, Oxford OX3 7LJ, England
关键词
prostate cancer; insulin-like growth factors type 1IGF receptor; chemosensitivity; apoptosis;
D O I
10.1046/j.1464-410X.2003.04061.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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. MATERIALIS 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.
引用
收藏
页码:271 / 277
页数:7
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