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A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

Authors
 Hyun Joo Lee  ;  Woo Kyung Lee  ;  Chan Woo Kang  ;  Cheol Ryong Ku  ;  Yoon Hee Cho  ;  Eun Jig Lee 
Citation
 Cancer Letters, Vol.417 : 131-140, 2018 
Journal Title
 Cancer Letters 
ISSN
 0304-3835 
Issue Date
2018
Keywords
CDK4 ; CDK6 ; LEE011 ; Retinoblastoma protein (RB) ; Thyroid cancer
Abstract
The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as FOXM1, Cyclin A1, and Myc in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162176
Full Text
https://www.sciencedirect.com/science/article/pii/S0304383518300107
DOI
10.1016/j.canlet.2017.12.037
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Institute of Endocrinology (내분비연구소)
Yonsei Authors
구철룡(Ku, Cheol Ryong) ORCID logo https://orcid.org/0000-0001-8693-9630
이우경(Lee, Woo Kyung) ORCID logo https://orcid.org/0000-0002-6737-3173
이은직(Lee, Eun Jig) ORCID logo https://orcid.org/0000-0002-9876-8370
조윤희(Cho, Yoon Hee)
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