Adachi Yusuke, Matsuki Masahiro, Watanabe Hideki, Takase Kazuma, Kodama Kotaro, Matsui Junji, Funahashi Yasuhiro, Nomoto Kenichi
a Tsukuba Research Laboratories , Eisai Co., Ltd , Ibaraki , Japan.
b Eisai Inc , Woodcliff Lake , New Jersey , USA.
Cancer Invest. 2019;37(4-5):185-198. doi: 10.1080/07357907.2019.1601209. Epub 2019 Apr 22.
High expression of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) is associated with poor prognosis. Here, we investigated the antitumor activity of lenvatinib, a multiple receptor tyrosine kinase inhibitor, in VEGF-overexpressing HCC models. In human umbilical vein endothelial cells, lenvatinib showed potent inhibitory activities against VEGF-induced proliferation and VEGF/basic fibroblast growth factor-induced tube formation. In VEGF-overexpressing HCC xenograft models, characterized by aggressive tumor growth and hypervascularity, lenvatinib had significant antitumor and antiangiogenic activities. These results suggest that potent activity of lenvatinib against VEGF signaling underlies its antitumor and antiangiogenic activities in the hypervascular HCC models.
血管内皮生长因子（VEGF）在肝细胞癌（HCC）患者中的高表达与预后不良相关。在此，我们研究了多受体酪氨酸激酶抑制剂乐伐替尼在VEGF过表达的HCC模型中的抗肿瘤活性。在人脐静脉内皮细胞中，乐伐替尼对VEGF诱导的增殖以及VEGF/碱性成纤维细胞生长因子诱导的管腔形成显示出强效抑制活性。在以侵袭性肿瘤生长和血管增生为特征的VEGF过表达的HCC异种移植模型中，乐伐替尼具有显著的抗肿瘤和抗血管生成活性。这些结果表明，乐伐替尼对VEGF信号的强效活性是其在高血管性HCC模型中具有抗肿瘤和抗血管生成活性的基础。
