目的:在不同类型的甲状腺癌中发现碘化物和葡萄糖摄取的替代方式,指的是触发器。ATC细胞表明低碘摄取和高葡萄糖摄取,缺乏高分化肿瘤的形态和遗传特征,并且变得越来越具有侵袭性。重要的是发现创新的多靶向药物来抑制癌症中失调的信号。在这项研究中,我们的目的是阐明芦丁作为植物药对基于碘和葡萄糖摄取的间变性甲状腺癌细胞系的分子机制。
方法:采用MTT测试来测试细胞活力。使用分光光度测定法进行碘化物摄取测定,以基于Sandell-Kolthoff反应确定SW1736细胞中的碘化物摄取。对于葡萄糖摄取检测,应用\'\'GOD-PAP\'\'酶比色测定法来测量细胞内的直接葡萄糖水平。NIS的测定,通过qRT-PCR进行SW1736细胞中GLUT1和3mRNA的表达。NIS的测定,SW1736细胞中的GLUT1和3蛋白水平通过蛋白质印迹进行。
结果:根据我们的结果,芦丁以时间和剂量依赖性方式抑制SW1736细胞的活力。定量实时RT-PCR分析显示,与对照组相比,芦丁处理组中NISmRNA水平增加。因此,Westernblot显示芦丁处理的SW1736细胞系中NIS蛋白高表达,GLUT1和3低表达。与对照组相比,芦丁增加了甲状腺癌细胞系SW1736中的碘摄取和葡萄糖摄取。
结论:多种机制表明芦丁作为碘化物摄取的主要刺激物和葡萄糖摄取的抑制剂,包括对NIS和GLUT的mRNA和蛋白质水平的影响,分别。在这里,我们将翻转现象描述为ATC的可能治疗靶点.此外,此处首先将芦丁记录为能够恢复SW1736细胞系中的细胞分化的NIS表达诱导物。还得出结论,GLUTs作为代谢靶标可以被芦丁特异性阻断,用于甲状腺癌的预防和治疗。
OBJECTIVE: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake.
METHODS: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, \'\'GOD-PAP\'\' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting.
RESULTS: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group.
CONCLUSIONS: Multiple mechanisms point to Rutin\'s role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.