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Updated: Aug 14, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor
G O Hellawell1, D J P Ferguson, S F Brewster
1Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Oxford OX3 9DS, UK.
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.
Insights
Downregulating type 1 insulin-like growth factor receptor (IGF1R) in prostate cancer cells enhances sensitivity to chemotherapy drugs like cisplatin. This suggests a potential new treatment strategy for advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer.
- IGF1R expression remains high in androgen-independent metastatic prostate cancer.
Purpose of the Study:
- To evaluate the impact of downregulating IGF1R on prostate cancer cell chemosensitivity.
- To explore IGF1R as a therapeutic target for chemoresistant prostate tumors.
Main Methods:
- Human androgen-independent DU145 prostate cancer cells were used.
- IGF1R was downregulated using antisense oligonucleotides or antisense RNA.
- Cells were treated with cisplatin, mitoxantrone, or paclitaxel, and survival was assessed via clonogenic assay.
Main Results:
- Antisense strategies reduced IGF1R protein levels by 50-70%.
- Chemosensitivity to cisplatin, mitoxantrone, and paclitaxel increased 1.5-2 fold.
- Cisplatin-induced apoptosis was enhanced.
Conclusions:
- Downregulating IGF1R increases prostate cancer cell sensitivity to chemotherapy.
- This strategy shows promise for treating advanced, chemoresistant prostate cancer.
- The approach may be applicable to other chemoresistant tumors.
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