奥拉诺芬作为治疗甲状腺无节细胞癌的新型抗癌药物

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2024-10-18 DOI:10.3390/ph17101394
Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An
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引用次数: 0

摘要

背景/目的:甲状腺无节细胞癌(ATC)是一种侵袭性罕见癌症,预后较差,传统疗法疗效有限。本研究对药物重新定位进行了研究,重点是将一种原本用于治疗类风湿性关节炎的金基药物奥拉诺芬(auranofin)作为治疗甲状腺癌的潜在药物。方法:从美国食品与药物管理局批准的药物库中确定了欧拉诺芬,并在两种甲状腺癌细胞系 8505C 和 FRO 上进行了测试。通过使用 Western 印迹、FACS 和 mRNA 测序进行基因和蛋白质表达分析,评估其抗肿瘤功效。采用裸鼠皮下注射法进行了体内实验,以确认欧拉诺芬的抗癌效果。结果欧拉诺芬可诱导活性氧(ROS)产生和细胞凋亡,导致细胞活力呈剂量依赖性降低、G1/S 期细胞周期停滞以及调节蛋白表达的改变。mRNA 测序显示,细胞外基质与受体相互作用途径发生了显著变化,Western 印迹结果也证实了这一点。体内异种移植模型显示出很强的抗肿瘤活性。结论欧拉诺芬有望成为一种治疗ATC的再利用药物,它能有效抑制细胞增殖、减少转移和促进细胞凋亡。这些研究结果表明,欧拉诺芬可在未来的 ATC 治疗策略中发挥关键作用。
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Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer.

Background/Objectives: Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. Methods: Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. Results: Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial-mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix-receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. Conclusions: Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies.

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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.
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