A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer Journal Article
| Authors: | Lin, S. F.; Lin, J. D.; Hsueh, C.; Chou, T. C.; Wong, R. J. |
| Article Title: | A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer |
| Abstract: | Background We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer. Materials and methods Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were measured by flow cytometry and fluorometric assay. Mice bearing flank anaplastic thyroid cancer (ATC) were treated with intraperitoneal injections of dinaciclib. Results Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner. Dinaciclib had a low median-effect dose (≤ 16.0 nM) to inhibit cell proliferation in seven thyroid cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-xL and survivin expression, activated caspase-3 and induced apoptosis. In vivo, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. Higher-dose dinaciclib (50 mg/kg) caused slight, but significant weight loss, which was absent with lower-dose dinaciclib (40 mg/kg) treatment. Conclusions Dinaciclib inhibited thyroid cancer proliferation both in vitro and in vivo. These findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer. © 2017 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Journal Title: | PLoS ONE |
| Volume: | 12 |
| Issue: | 2 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2017-02-16 |
| Start Page: | e0172315 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0172315 |
| PROVIDER: | scopus |
| PUBMED: | 28207834 |
| PMCID: | PMC5312924 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 March 2017 -- Source: Scopus |
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