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.
Keywords:
polo-like kinase inhibitor; sorafenib; volasertib; well-differentiated thyroid cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma, Follicular / drug therapy*
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Adenocarcinoma, Follicular / metabolism
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Adenocarcinoma, Follicular / pathology
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Benzimidazoles / administration & dosage
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Cell Cycle / drug effects
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Proliferation / drug effects
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Female
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Humans
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Mice
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Mice, Nude
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Polo-Like Kinase 1
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Protein Kinase Inhibitors / administration & dosage
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Pteridines / administration & dosage
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Sorafenib / administration & dosage
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Thiophenes / administration & dosage
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Thyroid Cancer, Papillary / drug therapy*
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Thyroid Cancer, Papillary / metabolism
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Thyroid Cancer, Papillary / pathology
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Thyroid Neoplasms / drug therapy*
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Thyroid Neoplasms / metabolism
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Thyroid Neoplasms / pathology
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Tumor Cells, Cultured
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Tumor Suppressor Proteins
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Xenograft Model Antitumor Assays
Substances
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BI 6727
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Benzimidazoles
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Cell Cycle Proteins
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GSK 461364
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Pteridines
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Thiophenes
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Tumor Suppressor Proteins
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Sorafenib
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PLK3 protein, human
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PLK2 protein, human
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Protein Serine-Threonine Kinases
Supplementary concepts
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Thyroid cancer, follicular