期刊
ENDOCRINE-RELATED CANCER
卷 25, 期 10, 页码 853-864出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-18-0150
关键词
roniciclib; cyclin-dependent kinase; well-differentiated thyroid cancer
资金
- Chang Gung Memorial Hospital [CMRPG3H0201, CMRPG3E0353]
- Ministry of Science and Technology of Taiwan [MOST 106-2314-B-182A-095]
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 in vivo 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 welldifferentiated thyroid cancer.
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