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替沃扎尼抑制甲状腺癌细胞和血管内皮细胞的增殖

郭丽娟, 郑岩, 刘鹏飞, 王恩彤

郭丽娟, 郑岩, 刘鹏飞, 王恩彤. 替沃扎尼抑制甲状腺癌细胞和血管内皮细胞的增殖[J]. 肿瘤防治研究, 2014, 41(09): 976-980. DOI: 10.3971/j.issn.1000-8578.2014.09.005
引用本文: 郭丽娟, 郑岩, 刘鹏飞, 王恩彤. 替沃扎尼抑制甲状腺癌细胞和血管内皮细胞的增殖[J]. 肿瘤防治研究, 2014, 41(09): 976-980. DOI: 10.3971/j.issn.1000-8578.2014.09.005
GUO Lijuan, ZHENG Yan, LIU Pengfei, WANG Entong. Tivozanib Inhibits Proliferation of Thyroid Cancer Cells and Vascular Endothelial Cells[J]. Cancer Research on Prevention and Treatment, 2014, 41(09): 976-980. DOI: 10.3971/j.issn.1000-8578.2014.09.005
Citation: GUO Lijuan, ZHENG Yan, LIU Pengfei, WANG Entong. Tivozanib Inhibits Proliferation of Thyroid Cancer Cells and Vascular Endothelial Cells[J]. Cancer Research on Prevention and Treatment, 2014, 41(09): 976-980. DOI: 10.3971/j.issn.1000-8578.2014.09.005

替沃扎尼抑制甲状腺癌细胞和血管内皮细胞的增殖

基金项目: 国家自然科学基金资助项目(30871268);北京市自然科学基金资助项目(3102029)
详细信息
    作者简介:

    郭丽娟(1987-),女,硕士在读,主要从事头颈肿瘤血管发生的研究

    通讯作者:

    王恩彤,E-mail:wang_entong@sina.com

  • 中图分类号: R736.1

Tivozanib Inhibits Proliferation of Thyroid Cancer Cells and Vascular Endothelial Cells

  • 摘要: 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。

     

    Abstract: Objective To investigate the effect of tivozanib, a novel tyrosine kinase inhibitor, on the proliferation of thyroid cancer cell line SW579 and vascular endothelial cell line HUVEC in vitro and the related 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 on cell proliferation were assessed by CCK-8 cell viability assay, cell imaging analysis and immunofluorescent staining of mitosis cells. Cell cycle analysis was performed by flow cytometry. Results Cell viability assay indicated that tivozanib inhibited the proliferation of both SW579 and HUVEC(P<0.05), in a time- and dosedependent manner, with median IC50 of 4 and 8 μM, respectively. Cell imaging analysis showed that tivozanib at IC50 significantly decreased cell densities of SW579 and HUVEC (P<0.05). Immunofluorescent staining of mitosis cells demonstrated that mitotic indexes of tivozanib-treated SW579 and HUVEC were decreased significantly (P<0.05). Flow cytometry demonstrated that tivozanib arrested SW579 and HUVEC at G1 and G2/M phases, respectively(P<0.05). Conclusion Tivozanib significantly inhibits the proliferation of SW579 and HUVEC by inducing cell cycle arrest at different phases. Tivozanib is indicated as a novel tyrosine kinase inhibitor for the treatment of thyroid cancer by targeting tumor cells and vascular endothelial cells.

     

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出版历程
  • 刊出日期:  2014-09-24

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