替沃扎尼抑制甲状腺癌细胞和血管内皮细胞的增殖

目的 研究新型酪氨酸激酶抑制剂替沃扎尼对甲状腺癌细胞株SW579和血管内皮细胞株HUVEC增殖的影响及作用机制。方法 SW579和HUVEC暴露于不同浓度（1、2、4、8和16 μM）的替沃扎尼至72 h，无药物处理的细胞作为对照。采用CCK-8细胞活度测定、图像分析技术及分裂细胞荧光免疫染色观察评价替沃扎尼对细胞增殖的影响，应用流式细胞仪进行细胞周期时相分析。结果细胞活度测定显示，替沃扎尼对两种细胞的生长增殖均有明显的抑制作用（P<0.05），并呈浓度依赖性及时间依赖性，两种细胞半数抑制浓度（IC50）分别约为4 μM和8 μM。图像分析显示，在IC50作用下，替沃扎尼使两种细胞的细胞密度降低，分裂指数下降（P<0.05）。细胞周期时相分析表明，替沃扎尼可使SW579和HUVEC发生细胞周期休止，但分别休止于G1期和G2/M期（P<0.05）。结论 替沃扎尼对甲状腺癌细胞和血管内皮细胞的增殖均有显著的抑制效应，其作用是籍细胞周期休止作用而实现，但在两种细胞所诱发的细胞周期休止时相不同。替沃扎尼作为一种新型酪氨酸激酶抑制剂可通过靶向癌细胞和血管内皮细胞来治疗甲状腺癌。

Tivozanib Inhibits Proliferation of Thyroid Cancer Cells and Vascular Endothelial Cells

Objective To investigate the effect of tivozanib, a novel tyrosine kinase inhibitor, on theproliferation of thyroid cancer cell line SW579 and vascular endothelial cell line HUVEC in vitro and therelated mechanisms. Methods SW579 and HUVEC were exposed to tivozanib at different concentration (1,2, 4, 8 and 16 μM) for 72 h, and tivozanib-untreated cells were taken as control. The effects of tivozanib oncell proliferation were assessed by CCK-8 cell viability assay, cell imaging analysis and immunofluorescentstaining of mitosis cells. Cell cycle analysis was performed by flow cytometry. Results Cell viability assayindicated that tivozanib inhibited the proliferation of both SW579 and HUVEC(P<0.05), in a time- and dosedependentmanner, with median IC50 of 4 and 8 μM, respectively. Cell imaging analysis showed that tivozanibat IC50 significantly decreased cell densities of SW579 and HUVEC (P<0.05). Immunofluorescent stainingof mitosis cells demonstrated that mitotic indexes of tivozanib-treated SW579 and HUVEC were decreasedsignificantly (P<0.05). Flow cytometry demonstrated that tivozanib arrested SW579 and HUVEC at G1 andG2/M phases, respectively(P<0.05). Conclusion Tivozanib significantly inhibits the proliferation of SW579and HUVEC by inducing cell cycle arrest at different phases. Tivozanib is indicated as a novel tyrosine kinaseinhibitor for the treatment of thyroid cancer by targeting tumor cells and vascular endothelial cells.