Division of Endocrinology & Metabolism, Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
Pharm Res. 2012 Jul;29(7):1990-2005. doi: 10.1007/s11095-012-0727-3. Epub 2012 Apr 4.
A novel and effective treatment is urgently needed to deal with the current treatment dilemma in incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been shown to be effective in tumor suppression.
We performed in vitro evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines, respectively.
Treatment of these three lines with reversine inhibited proliferation in a time- and dose-dependent manner. G2/M accumulation was demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase inhibitor before treatment with reversine attenuated cell death. Reversine also showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice model.
Data demonstrated that reversine is effective in inhibiting the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria-independent pathway. Reversine is therefore worthy of further investigation in clinical therapeutics.
目前无法治愈的分化型甲状腺癌（DTC）、低分化甲状腺癌（PDTC）和间变性甲状腺癌（ATC）的治疗困境亟待一种新的有效治疗方法。雷维塞宁是一种新型有效的治疗方法，它是一种有效的肿瘤抑制小分子合成嘌呤类似物（2,6-二取代嘌呤）。
我们分别在体外评估了雷维塞宁对人 PDTC、ATC 和滤泡性甲状腺癌细胞系增殖、细胞周期和凋亡的抗肿瘤作用。
雷维塞宁处理这三种细胞系，可呈时间和剂量依赖性抑制增殖。细胞周期分析显示 G2/M 期积累。雷维塞宁诱导 PDTC 细胞凋亡，同时激活 caspase-3 和 caspase-8，但不激活 caspase-9。用泛 caspase 抑制剂预处理雷维塞宁可减轻细胞死亡。雷维塞宁还在 ATC 细胞的异种移植裸鼠模型中显示出体内生长抑制作用。
数据表明，雷维塞宁通过细胞周期阻滞或凋亡有效抑制甲状腺癌细胞的生长，特别是更具侵袭性的 ATC 和 PDTC。细胞凋亡是由线粒体非依赖性途径诱导的。因此，雷维塞宁值得进一步研究用于临床治疗。
