Effects of Pazopanib Monotherapy vs. Pazopanib and Topotecan Combination on Anaplastic Thyroid Cancer Cells
Effects of Pazopanib Monotherapy vs. Pazopanib and Topotecan Combination on Anaplastic Thyroid Cancer Cells
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DOI：
10.3389/fonc.2019.01202
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发表时间：
2019-11-12
影响因子：
4.7
通讯作者：
Bocci, Guido
中科院分区：
文献类型：
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作者：
Di Desidero, Teresa;Orlandi, Paola;Bocci, Guido
本研究的目的是检查帕唑帕尼/托泊替康组合与帕唑帕尼单药治疗对未分化甲状腺癌（ATC）细胞的活性。对单独给予帕唑帕尼和托泊替康以及同时给予帕唑帕尼和托泊替康联合给药72小时的ATC细胞系进行增殖分析。帕唑帕尼和拓扑替康对ATC细胞产生了强烈的协同作用，通过组合指数计算，增加了通过高效液相色谱法测量的拓扑替康内酯的细胞内浓度。此外，通过真实的时间PCR测试，在联合处理的ATC细胞中，ATP结合盒转运体G2（ABCG-2）、血管内皮生长因子（VEGF）、缺氧诱导因子-1 α（HIF-1 α）和集落刺激因子-1（CSF-1）的基因表达显著降低。总之，帕唑帕尼和拓扑替康的同时联合建立了高度协同的ATC抗增殖作用，这表明将该方案转化为临床试验的新可能性。
The purpose of this study was to examine pazopanib/topotecan combination activity vs. pazopanib monotherapy on anaplastic thyroid cancer (ATC) cells. Proliferation analyses were performed on ATC cell lines administered for 72 h with pazopanib and topotecan alone and to their simultaneous combination. Pazopanib and topotecan produced a strong synergism on ATC cells, calculated by the combination index, increasing the intracellular concentrations of topotecan lactone measured by high-performance liquid chromatography. Furthermore, a significantly decrease of the gene expression of ATP-binding cassette transporter G2 (ABCG-2), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and colony stimulating factor-1 (CSF-1) was presented in combination-treated ATC cells by real time PCR tests. In summary, the simultaneous association of pazopanib and topotecan established a highly synergistic ATC antiproliferative effect, suggesting a new possibility to translate this schedule into clinical trials.