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Endocr Relat Cancer. 2019 Jun 1. pii: ERC-18-0555.R2. doi: 10.1530/ERC-18-0555. [Epub ahead of print]

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

Author information

1
S Lin, Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
2
J Lin, Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
3
C Yeh, General Surgery Department, Chang Gung Memorial Hospital, Taoyuang, Taiwan.
4
Y Huang, Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan.
5
T Chou, Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, United States.
6
R Wong, Surgery, Memorial Sloan-Kettering Cancer Center, New York, United States.

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) 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 S phase and increased cells in 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 either single treatment 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 well-differentiated thyroid cancer.

PMID:
31189135
DOI:
10.1530/ERC-18-0555

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