Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model.
Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model.
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DOI：
10.1002/hed.21455
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发表时间：
2011-03
影响因子：
2.9
通讯作者：
Myers, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Sano, Daisuke;Fooshee, David R.;Zhao, Mei;Andrews, Genevieve A.;Frederick, Mitchell J.;Galer, Chad;Milas, Zvonimir L.;Morrow, Phuong Khanh H.;Myers, Jeffrey N.
关键词：
我们研究了凡德他尼（一种血管内皮生长因子受体2（VEGFR-2）和表皮生长因子受体（EGFR）的抑制剂）单独使用以及与紫杉醇联合使用在人头颈部鳞状细胞癌（HNSCC）原位小鼠模型中的作用。在两种HNSCC细胞系中评估了凡德他尼（ZACTIMA™）对细胞生长、凋亡以及受体和下游信号传导分子表达和磷酸化水平的体外作用。我们通过测量肿瘤细胞凋亡、内皮细胞凋亡、微血管密度、肿瘤大小和动物存活率来评估凡德他尼和/或紫杉醇的体内作用。在体外，凡德他尼抑制HNSCC细胞中EGFR及其下游靶点的磷酸化，抑制HNSCC细胞的增殖并诱导细胞凋亡，延长原位注射人HNSCC的裸鼠的存活期并抑制肿瘤生长。凡德他尼有望成为HNSCC的新型分子靶向治疗药物。
We investigated the effects of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR), alone and in combination with paclitaxel in an orthotopic mouse model of human head and neck squamous cell carcinoma (HNSCC). The in vitro effects of vandetanib (ZACTIMA™) were assessed in two HNSCC cell lines on cell growth, apoptosis, and receptor and downstream signaling morecule expression and phosphorylation levels. We assessed in vivo effects of vandetanib and/or paclitaxel by measuring tumor cell apoptosis, endothelial cell apoptosis, microvessel density, tumor size, and animal survival. In vitro, vandetanib inhibited the phosphorylation of EGFR and its downstream targets in HNSCC cells and inhibited proliferation and induced apoptosis of HNSCC cells and extended survival and inhibited tumor growth in nude mice orthotopically injected with human HNSCC. Vandetanib has the potential to be a novel molecular targeted therapy for HNSCC.
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