SW1736无性甲状腺癌细胞系中碘-葡萄糖翻转的调控。

IF 5.4 2区 医学 Q1 Medicine Journal of Endocrinological Investigation Pub Date : 2024-11-01 Epub Date: 2024-05-02 DOI:10.1007/s40618-024-02377-4
S Heydarzadeh, A A Moshtaghie, M Daneshpour, M Hedayati
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引用次数: 0

摘要

目的和背景:在不同类型的甲状腺癌中发现了碘和葡萄糖摄取的另一种方式,即 "翻转"(flip-flop)。ATC 细胞碘摄取量低而葡萄糖摄取量高,缺乏分化良好肿瘤的形态和遗传特征,侵袭性越来越强。发现创新的多靶点药物来抑制癌症中失调的信号传导,具有重要意义。在这项研究中,我们旨在根据碘化物和葡萄糖的摄取,阐明芦丁作为一种植物药对无性甲状腺癌细胞株的分子机制:材料方法:采用MTT试验检测细胞活力。碘吸收检测采用分光光度法,根据桑德尔-科尔索夫反应测定 SW1736 细胞对碘的吸收。葡萄糖吸收检测采用 "GOD-PAP "酶比色法,直接测定细胞内的葡萄糖水平。采用 qRT-PCR 技术检测 SW1736 细胞中 NIS、GLUT1 和 3 mRNA 的表达。用 Western 印迹法测定 SW1736 细胞中 NIS、GLUT1 和 3 蛋白水平:结果:芦丁对 SW1736 细胞活力的抑制具有时间和剂量依赖性。Real-time RT-PCR 定量分析显示,与对照组相比,芦丁处理组的 NIS mRNA 水平升高。相应地,Western 印迹显示芦丁处理的 SW1736 细胞株中 NIS 蛋白高表达,而 GLUT 1 和 3 低表达。与对照组相比,芦丁提高了甲状腺癌细胞株 SW1736 的碘摄取量,降低了葡萄糖摄取量:多种机制表明,芦丁是碘摄取的主要刺激剂和葡萄糖摄取的抑制剂,包括在 mRNA 和蛋白质水平分别对 NIS 和 GLUTs 产生影响。在这里,我们将翻转现象描述为一种可能的 ATC 治疗靶点。此外,本文首次证实芦丁是一种 NIS 表达诱导剂,能够恢复 SW1736 细胞系的细胞分化。由此也可以得出结论,芦丁可以特异性地阻断作为代谢靶点的GLUTs,从而达到预防和治疗甲状腺癌的目的。
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Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.

Aims and background: 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.

Material 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.

Conclusion: 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.

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来源期刊
Journal of Endocrinological Investigation
Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
8.10
自引率
7.40%
发文量
242
期刊介绍: The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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