Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer. Academic Article uri icon

Overview

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.

publication date

  • August 1, 2019

Research

keywords

  • Adenocarcinoma, Follicular
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Cycle Proteins
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms

Identity

PubMed Central ID

  • PMC7475022

Scopus Document Identifier

  • 85068851511

Digital Object Identifier (DOI)

  • 10.1530/ERC-18-0555

PubMed ID

  • 31189135

Additional Document Info

volume

  • 26

issue

  • 8