Metere Alessio, Frezzotti Francesca, Graves Claire Elizabeth, Vergine Massimo, De Luca Alessandro, Pietraforte Donatella, Giacomelli Laura
1Department of Surgical Sciences, Umberto I Hospital, "Sapienza" University of Rome, viale Regina Elena 324, 00161 Rome, Italy.
2Department of Surgery, Columbia University Medical Center, New York, USA.
Cancer Cell Int. 2018 Jan 15;18:7. doi: 10.1186/s12935-018-0504-4. eCollection 2018.
Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells.
Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique.
Our results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2% respectively, p < 0.01) in the thyroid cancer cells compared to the healthy cells. In addition, the EPR technique shows an increase of free radicals in tumor tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%, p < 0.01).
Our findings underscore the relationship between thyroid cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant system in thyroid cancer tissue. These results suggest that either the inability to produce adequate antioxidant defense or an increased consumption of antioxidants, due to the hyper-production of free radicals, may play a crucial role in thyroid cancer.
氧化应激会导致蛋白质、脂质和DNA的化学结构发生某些改变，进而影响其功能。最近的研究将氧化应激与癌症，尤其是甲状腺癌联系起来，但具体机制仍不清楚。在此，我们通过分析两种硒抗氧化分子——谷胱甘肽过氧化物酶（GPx1）和硫氧还蛋白还原酶（TrxR1）在甲状腺癌细胞中的表达，进一步明确氧化应激在甲状腺癌中的作用。
在全甲状腺切除术后，采集健康甲状腺组织和甲状腺肿瘤样本进行分析。通过蛋白质免疫印迹分析揭示GPx1和TrxR1的表达情况，并通过光密度分析进行定量，同时采用电子顺磁共振（EPR）自旋捕获技术评估自由基。
我们的结果显示，与健康细胞相比，甲状腺癌细胞中GPx1和TrxR1的表达下降（分别下降45.7%和43.2%，p<0.01）。此外，EPR技术显示肿瘤组织中的自由基增加，显著高于健康甲状腺组织（增加116.3%，p<0.01）。
我们的研究结果强调了甲状腺癌与氧化应激之间的关系，表明甲状腺癌组织中氧化/抗氧化系统失衡。这些结果表明，要么是无法产生足够的抗氧化防御，要么是由于自由基的过量产生导致抗氧化剂消耗增加，可能在甲状腺癌中起关键作用。
