Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1788-1798 |
Number of pages | 11 |
Journal | Prostate |
Volume | 66 |
Issue number | 16 |
DOIs | |
State | Published - Dec 1 2006 |
Keywords
- Angiogenesis
- Antivascular therapy
- Chemotherapy resistant
- EGF-R and VEGF-R phosphorylation
- Multidrug resistant
- Prostate cancer
ASJC Scopus subject areas
- Oncology
- Urology