구강 편평상피세포암 동위종양 모델에서 내피세포의 수용체 타이로신 인산화효소에 대한 표적치료

TARGETING RECEPTOR TYROSINE KINASE ON ENDOTHELIAL CELLS IN AN ORTHOTOPIC TUMOR MODEL OF ORAL SQUAMOUS CELL CARCINORMA

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor (orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators (pMAPK and pAkt), decreased proliferative index, decreased microvessel density (MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC