Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States.
Head Neck. 2012 Sep;34(9):1269-76. doi: 10.1002/hed.21917. Epub 2012 Feb 6.
The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) have been implicated as therapeutic targets for head and neck squamous cell carcinoma (HNSCC). Vandetanib is a small-molecule tyrosine kinase inhibitor (TKI) with dual specificity for EGFR and VEGFR. Here we characterize the phenotypic and biochemical effects of vandetanib on various HNSCC cell lines.
In vitro models were used for studying tumor cell viability, invasion, and signaling as well as in vivo xenograft models.
Treatment with vandetanib reduced viability, invasion, and tumor growth of HNSCC cell lines. Phosphorylation levels of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) were reduced in vandetanib-treated HNSCC cells. Additionally, vandetanib abrogates EGF-induced STAT3 activity and STAT3 target gene expression.
We demonstrated that vandetanib inhibits the growth of head and neck cancer cell lines. The antitumor effects of vandetanib appear to be exerted via the EGFR inhibitory effect of the compound.
表皮生长因子受体（EGFR）和血管内皮生长因子受体（VEGFR）已被认为是头颈部鳞状细胞癌（HNSCC）的治疗靶点。凡德他尼是一种小分子酪氨酸激酶抑制剂（TKI），对 EGFR 和 VEGFR 具有双重特异性。在这里，我们描述了凡德他尼对各种 HNSCC 细胞系的表型和生化作用。
使用体外模型研究肿瘤细胞活力、侵袭和信号转导以及体内异种移植模型。
凡德他尼治疗降低了 HNSCC 细胞系的活力、侵袭和肿瘤生长。凡德他尼处理的 HNSCC 细胞中丝裂原活化蛋白激酶（MAPK）和信号转导和转录激活因子 3（STAT3）的磷酸化水平降低。此外，凡德他尼阻断了 EGF 诱导的 STAT3 活性和 STAT3 靶基因表达。
我们证明了凡德他尼抑制头颈部癌细胞系的生长。凡德他尼的抗肿瘤作用似乎是通过该化合物对 EGFR 的抑制作用发挥的。
