Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor.
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-indepen...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1826276340947484672 |
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| author | Hellawell, G Ferguson, D Brewster, S Macaulay, V |
| author_facet | Hellawell, G Ferguson, D Brewster, S Macaulay, V |
| author_sort | Hellawell, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:12:29Z |
| format | Journal article |
| id | oxford-uuid:65f62036-a238-4f11-a987-42273db982a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:12:29Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:65f62036-a238-4f11-a987-42273db982a72022-03-26T18:28:54ZChemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:65f62036-a238-4f11-a987-42273db982a7EnglishSymplectic Elements at Oxford2003Hellawell, GFerguson, DBrewster, SMacaulay, VOBJECTIVE: 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. |
| spellingShingle | Hellawell, G Ferguson, D Brewster, S Macaulay, V Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title | Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title_full | Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title_fullStr | Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title_full_unstemmed | Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title_short | Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. |
| title_sort | chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin like growth factor receptor |
| work_keys_str_mv | AT hellawellg chemosensitizationofhumanprostatecancerusingantisenseagentstargetingthetype1insulinlikegrowthfactorreceptor AT fergusond chemosensitizationofhumanprostatecancerusingantisenseagentstargetingthetype1insulinlikegrowthfactorreceptor AT brewsters chemosensitizationofhumanprostatecancerusingantisenseagentstargetingthetype1insulinlikegrowthfactorreceptor AT macaulayv chemosensitizationofhumanprostatecancerusingantisenseagentstargetingthetype1insulinlikegrowthfactorreceptor |