Dual Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation by AEE788 Reduces Growth and Metastasis of Human Colon Carcinoma in an Orthotopic Nude Mouse Model

摘要: We studied growth factors and their receptors in tumor cells tumor-associated endothelial as the therapeutic targets colon cancer. Immunohistochemical analysis of 13 surgical specimens human adenocarcinoma revealed that both 11 expressed epidermal factor (EGF), transforming alpha (TGF-alpha), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), vascular (VEGF), VEGF (VEGFR), VEGFR (pVEGFR). HT29 cancer growing orthotopically cecum nude mice a high level EGF, EGFR, pEGFR, VEGF, VEGFR, pVEGFR. Double-immunofluorescence staining found mouse also pEGFR Tumors treated for 5 weeks with oral AEE788 (an inhibitor tyrosine kinase) single agent or CPT-11 alone were smaller (>50%) than those control mice. Mice combination had significantly tumors (P < 0.01) complete inhibition lymph node metastasis. inhibited pVEGFR, Akt expression on well cells. The therapy decreased microvessel density cell proliferation increased apoptosis Collectively, these data suggest dual signaling pathways chemotherapy can provide new approach to treatment