An Seung-Chan, Jun Hak Hoon, Kim Kyeong Mi, Kim Issac, Choi Sujin, Yeo Hyunjeong, Lee Soonchul, An Hyun-Ju
Department of Orthopaedic Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea.
Department of General Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea.
Pharmaceuticals (Basel). 2024 Oct 18;17(10):1394. doi: 10.3390/ph17101394.
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. 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. 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. 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.
间变性甲状腺癌(ATC)是一种侵袭性强且罕见的癌症,预后较差,传统疗法疗效有限。本研究调查药物重新定位,重点关注金诺芬,一种最初用于治疗类风湿性关节炎的金基药物,作为ATC的潜在治疗方法。金诺芬是从美国食品药品监督管理局(FDA)批准的药物库中筛选出来的,并在两种甲状腺癌细胞系8505C和FRO上进行了测试。通过蛋白质免疫印迹法(Western blot)、荧光激活细胞分选术(FACS)和mRNA测序对基因和蛋白质表达进行分析,评估其抗肿瘤疗效。采用裸鼠皮下注射进行体内实验,以证实金诺芬的抗癌作用。金诺芬可诱导活性氧(ROS)生成和细胞凋亡,导致细胞活力呈剂量依赖性降低、G1/S期细胞周期阻滞以及调节蛋白表达改变。它还抑制癌症干细胞活性并抑制上皮-间质转化。mRNA测序显示细胞外基质-受体相互作用途径发生显著变化,蛋白质免疫印迹结果也证实了这一点。体内异种移植模型显示出强大的抗肿瘤活性。金诺芬作为一种重新利用的ATC治疗药物具有潜力,可有效抑制细胞增殖、减少转移并促进细胞凋亡。这些发现表明金诺芬可能在未来的ATC治疗策略中发挥关键作用。