Therapy of multidrug resistant human prostate tumors in the prostate of nude mice by simultaneous targeting of the epidermal growth factor receptor and vascular endothelial growth factor receptor on tumor-associated endothelial cells
| Autor: | Sertac Yazici, J. Erik Busby, Kim Anh Do, Isaiah J. Fidler, Marva Maya, Toru Nakamura, Sun Jin Kim, Junqin He, Jang Seong Kim, Dominic Fan, Xuemei Wang |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Paclitaxel Angiogenesis Urology Mice Nude Apoptosis Vascular endothelial growth inhibitor Mice Nude mouse Growth factor receptor Epidermal growth factor Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine In Situ Nick-End Labeling Animals Humans Growth factor receptor inhibitor AEE788 Epidermal growth factor receptor Phosphorylation biology business.industry Endothelial Cells Prostatic Neoplasms biology.organism_classification Xenograft Model Antitumor Assays Drug Resistance Multiple ErbB Receptors Endocrinology Receptors Vascular Endothelial Growth Factor Oncology Drug Resistance Neoplasm Purines Lymphatic Metastasis Cancer research biology.protein business |
| Zdroj: | The Prostate. 66(16) |
| ISSN: | 0270-4137 |
| Popis: | BACKGROUND Inhibiting epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) activation with AEE788 can decrease prostate cancer (CaP) growth/progression. We determined whether tumor cells or tumor-associated endothelial cells were the primary target by treating multidrug-resistant (MDR) CaP growing in the prostate of nude mice. METHODS MDR human CaP cells with 30-fold increased taxane-resistance were implanted into nude mouse prostates. After 2 weeks, mice were randomized to control, paclitaxel, AEE788, and AEE788/paclitaxel for 10 weeks. Mice were necropsied and tumors stained. RESULTS AEE788 or AEE788 plus paclitaxel significantly reduced tumor incidence and tumor weight, and eradicated lymph node metastasis. Inhibiting VEGF-R and EGF-R phosphorylation induced apoptosis of tumor-associated endothelial cells causing a second apoptotic wave of surrounding tumor cells. CONCLUSION Inhibiting VEGF-R and EGF-R activation on tumor-associated endothelial cells with AEE788 combined with paclitaxel can bypass CaP cell resistance and prevent lymph node metastasis. Prostate © 2006 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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