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白藜芦醇增加了大鼠甲状腺细胞系 FRTL-5 中的碘捕获。

Resveratrol increases iodide trapping in the rat thyroid cell line FRTL-5.

机构信息

INSERM UMR-911 and Research Center in Biological and Oncopharmacological Oncology (CrO2), School of Medicine-Timone, Aix-Marseille University, France.

出版信息

Thyroid. 2010 Feb;20(2):195-203. doi: 10.1089/thy.2009.0171.

Abstract

BACKGROUND

Resveratrol, a polyphenol found in grapes, exhibits several beneficial health effects by its antioxidant, antiinflammatory, and chemopreventive properties. The aim of the present study was to determine the effect of resveratrol on iodide trapping and efflux as well as its mode of action using FRTL-5 cells, having in mind the pivotal role of the natrium iodide symporter (NIS) in the treatment of differentiated thyroid cancers.

METHODS

Cells were treated with resveratrol for various times and doses, in the presence or absence of thyrotropin (TSH). Iodide trapping, iodide efflux, rat NIS (rNIS) protein expression, and cyclic AMP (cAMP) production were evaluated.

RESULTS

Resveratrol increased iodide trapping in a time-dependent (optimal 6 hours) and dose-dependent (100 microM) way in the presence of TSH. It showed an additive effect when concomitantly added with an optimal dose of TSH. Resveratrol (50 microM) increased (threefold) rNIS protein expression. In TSH-deprived cells, resveratrol also provoked an increase in rNIS protein (>3-fold in 6 hours) with an optimum at 40 microM. Resveratrol did not inhibit iodide efflux from FRTL-5 cells. It neither increased intracellular cAMP nor induced the arborization of living cells, two TSH-induced effects. A non-cAMP mode of action is highly suspected.

CONCLUSIONS

Resveratrol increases iodide trapping in FRTL-5 cells, increasing iodide influx and rNIS protein level even in the absence of TSH. It has an additive effect with TSH. Consequently, resveratrol could be a promising molecule for radioiodide therapy in follicular and papillary differentiated thyroid carcinoma in association with recombinant human TSH.

摘要

背景

白藜芦醇是一种存在于葡萄中的多酚,具有抗氧化、抗炎和化学预防特性,表现出多种有益的健康作用。本研究的目的是确定白藜芦醇对碘捕获和外排的影响及其作用模式,考虑到钠碘转运体(NIS)在分化型甲状腺癌治疗中的关键作用。

方法

用白藜芦醇处理 FRTL-5 细胞,不同时间和剂量,有或没有促甲状腺激素(TSH)。评估碘捕获、碘外排、大鼠 NIS(rNIS)蛋白表达和环磷酸腺苷(cAMP)产生。

结果

在 TSH 存在的情况下,白藜芦醇以时间依赖性(最佳 6 小时)和剂量依赖性(100μM)方式增加碘捕获。当与最佳剂量的 TSH 同时添加时,表现出相加作用。白藜芦醇(50μM)增加(三倍)rNIS 蛋白表达。在 TSH 剥夺的细胞中,白藜芦醇也引起 rNIS 蛋白增加(6 小时增加 3 倍),最佳浓度为 40μM。白藜芦醇不抑制 FRTL-5 细胞的碘外排。它也不增加细胞内 cAMP,也不诱导活细胞的分支,这是 TSH 诱导的两种效应。高度怀疑存在非 cAMP 作用模式。

结论

白藜芦醇增加 FRTL-5 细胞的碘捕获,增加碘内流和 rNIS 蛋白水平,即使在没有 TSH 的情况下也是如此。它与 TSH 具有相加作用。因此,白藜芦醇可能是与重组人 TSH 联合用于滤泡性和乳头状分化型甲状腺癌放射性碘治疗的有前途的分子。

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