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

作者: S. Yazici , S.J. Kim , J.E. Busby , J. He , P. Thaker

DOI: 10.1002/PROS.20283

关键词: Prostate cancerTumor microenvironmentEpidermal growth factorCancer researchMetastasisAEE788CancerEndocrinologyInternal medicineEpidermal growth factor receptorMedicineVascular endothelial growth factor

摘要: BACKGROUND Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tumor microenvironment. We determined whether a dual tyrosine kinase inhibitor (AEE788) epidermal growth factor receptor (EGF-R) and vascular endothelial (VEGF-R) combined with chemotherapy can produce therapy human PCa in nude mice. METHODS PC-3MM2 cells were injected into mice. Three days later, mice randomized four groups: saline control, paclitaxel, AEE788, AEE788 paclitaxel. The treated for 5 weeks necropsied. Tumor incidence, weight, incidence lymph node metastasis recorded. tissue was analyzed immunohistochemically. RESULTS Treatment or plus paclitaxel significantly decreased total metastasis. treatment alone combination inhibited phosphorylation EGF-R VEGF-R on tumor-associated cells. Therapeutic efficacy correlated an increase apoptosis cells. CONCLUSION Blockade signaling pathways coupled suppressed progressive growing orthotopically © 2005 Wiley-Liss, Inc.

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