Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer Journal Article
| Authors: | Lin, S. F.; Lin, J. D.; Yeh, C. N.; Huang, Y. T.; Chou, T. C.; Wong, R. J. |
| Article Title: | Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer |
| Abstract: | Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC. © 2019 Society for Endocrinology. |
| Keywords: | sorafenib; cancer; volasertib; polo-like kinase inhibitor; well-differentiated thyroid |
| Journal Title: | Endocrine-Related Cancer |
| Volume: | 26 |
| Issue: | 8 |
| ISSN: | 1351-0088 |
| Publisher: | Bioscientifica Ltd |
| Date Published: | 2019-06-01 |
| Start Page: | 727 |
| End Page: | 738 |
| Language: | English |
| DOI: | 10.1530/erc-18-0555 |
| PUBMED: | 31189135 |
| PROVIDER: | scopus |
| PMCID: | PMC7475022 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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