Dual inhibition of the epidermal growth factor and vascular endothelial growth factor phosphorylation for antivascular therapy of human prostate cancer in the prostate of nude mice

Autor: Premal H. Thaker, Junquin He, Sertac Yazici, Isaiah J. Fidler, Dominic Fan, Kenji Yokoi, Sun Jin Kim, J. E. Busby
Rok vydání: 2005
Předmět:
Male
medicine.medical_specialty
Paclitaxel
Urology
Mice
Nude
Apoptosis
Cell Growth Processes
Metastasis
Capillary Permeability
Prostate cancer
chemistry.chemical_compound
Mice
Epidermal growth factor
Internal medicine
Cell Line
Tumor
medicine
In Situ Nick-End Labeling
Animals
Humans
AEE788
Epidermal growth factor receptor
Phosphorylation
Protein Kinase Inhibitors
Tumor microenvironment
biology
Neovascularization
Pathologic
business.industry
Cancer
Prostatic Neoplasms
medicine.disease
Antineoplastic Agents
Phytogenic
Xenograft Model Antitumor Assays
Vascular endothelial growth factor
ErbB Receptors
Platelet Endothelial Cell Adhesion Molecule-1
Endocrinology
Receptors
Vascular Endothelial Growth Factor
Oncology
chemistry
Microscopy
Fluorescence
Purines
Cancer research
biology.protein
business
Zdroj: The Prostate. 65(3)
ISSN: 0270-4137
Popis: BACKGROUND Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tumor microenvironment. We determined whether a dual tyrosine kinase inhibitor (AEE788) of the epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) combined with chemotherapy can produce therapy of human PCa in nude mice. METHODS PC-3MM2 human PCa cells were injected into the prostate of nude mice. Three days later, the mice were randomized into four groups: saline control, paclitaxel, AEE788, and AEE788 and paclitaxel. The mice were treated for 5 weeks and necropsied. Tumor incidence, weight, and incidence of lymph node metastasis were recorded. Tumor tissue was analyzed immunohistochemically. RESULTS Treatment of mice with AEE788 or AEE788 plus paclitaxel significantly decreased tumor incidence, total tumor weight, and incidence of lymph node metastasis. AEE788 treatment alone or in combination with paclitaxel inhibited the phosphorylation of EGF-R and VEGF-R on tumor cells and tumor-associated endothelial cells. Therapeutic efficacy correlated with an increase in apoptosis of tumor cells and tumor-associated endothelial cells. CONCLUSION Blockade of EGF-R and VEGF-R signaling pathways coupled with chemotherapy suppressed the progressive growth and metastasis of human PCa cells growing orthotopically in nude mice. © 2005 Wiley-Liss, Inc.
Databáze: OpenAIRE
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