伦瓦提尼
甲状腺间变性癌
癌症研究
癌基因
甲状腺癌
癌症
医学
细胞生长
细胞周期
细胞凋亡
内科学
药理学
生物
遗传学
生物化学
作者
Silvia Ferrari,Guido Bocci,Teresa Di Desidero,Giusy Elia,Ilaria Ruffilli,Francesca Ragusa,Paola Orlandi,Sabrina Rosaria Paparo,Armando Patrizio,Simona Piaggi,Concettina La Motta,Salvatore Ulisse,Enke Baldini,Gabriele Materazzi,Paolo Miccoli,Alessandro Antonelli,Poupak Fallahi
摘要
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages. The effect of lenvatinib (1 and 100 nM; and 1, 10, 25 and 50 µM) was investigated in primary ATC, 8305C and AF cells as well as in AF cells in CD nu/nu mice. Lenvatinib significantly reduced ATC cell proliferation (P<0.01, ANOVA) and increased the percentage of apoptotic ATC cells (P<0.001, ANOVA). Furthermore, lenvatinib inhibited migration (P<0.01) and invasion (P<0.001) in ATC. In addition, lenvatinib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in the ATC cells. Lenvatinib also significantly inhibited 8305C and AF cell proliferation, increasing apoptosis. AF cells were subcutaneously injected into CD nu/nu mice and tumor masses were observed 20 days later. Tumor growth was significantly inhibited by lenvatinib (25 mg/kg/day), as well as the expression of VEGF-A and microvessel density in the AF tumor tissues. In conclusion, the antitumor and antiangiogenic activities of lenvatinib may be promising for the treatment of anaplastic thyroid cancer, and may consist a basis for future clinical therapeutic applications.
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