Department of Internal MedicineChang Gung Memorial Hospital, Taoyuan, Taiwan
Chang Gung UniversityTaoyuan, Taiwan.
Endocr Relat Cancer. 2018 Oct;25(10):853-864. doi: 10.1530/ERC-18-0150. Epub 2018 Jun 12.
Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in the G2/M phase. Roniciclib treatment retarded the growth of two well-differentiated thyroid tumors in xenograft models in a dose-dependent fashion. Furthermore, the combination of roniciclib with sorafenib was more effective than either single treatment in a follicular thyroid cancer xenograft model. Acceptable safety profiles appeared in animals treated with either roniciclib alone or roniciclib and sorafenib combination therapy. These findings support roniciclib as a potential drug for the treatment of patients with well-differentiated thyroid cancer.
细胞周期蛋白依赖性激酶活性的激活在许多人类癌症中经常观察到；因此，促进细胞周期过渡和细胞增殖的细胞周期蛋白依赖性激酶可能是治疗恶性肿瘤的潜在靶点。本研究探讨了罗尼克利布（一种针对甲状腺乳头癌和滤泡癌的细胞周期蛋白依赖性激酶抑制剂，指定为分化良好的甲状腺癌）的治疗效果。罗尼克利布以剂量依赖性方式抑制两种甲状腺乳头癌和两种甲状腺滤泡癌细胞系的细胞增殖。罗尼克利布激活半胱天冬酶-3 活性并诱导细胞凋亡。细胞周期进程被阻滞在 G2/M 期。罗尼克利布以剂量依赖性方式延迟异种移植模型中两种分化良好的甲状腺肿瘤的生长。此外，罗尼克利布与索拉非尼联合治疗在甲状腺滤泡癌异种移植模型中的效果优于单一治疗。单独使用罗尼克利布或罗尼克利布联合索拉非尼治疗的动物的安全性状况可以接受。这些发现支持罗尼克利布作为治疗分化良好的甲状腺癌患者的潜在药物。
