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

Hyun Joo Lee, Woo Kyung Lee, Chan Woo Kang, Cheol Ryong Ku, Yoon Hee Cho, Eunjig Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)131-140
Number of pages10
JournalCancer Letters
Volume417
DOIs
Publication statusPublished - 2018 Mar 28

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Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Thyroid Neoplasms
Cell Proliferation
Apoptosis
Cyclin D
Cell Line
Cell Cycle Checkpoints
Cyclin A1
Phosphorylation
Cell Cycle Resting Phase
Cyclin-Dependent Kinases
G1 Phase
Heterografts
Oral Administration
Neoplasms
Thyroid Gland
Carcinogenesis
Western Blotting
ribociclib

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lee, Hyun Joo ; Lee, Woo Kyung ; Kang, Chan Woo ; Ku, Cheol Ryong ; Cho, Yoon Hee ; Lee, Eunjig. / A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer. In: Cancer Letters. 2018 ; Vol. 417. pp. 131-140.
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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. / Lee, Hyun Joo; Lee, Woo Kyung; Kang, Chan Woo; Ku, Cheol Ryong; Cho, Yoon Hee; Lee, Eunjig.

In: Cancer Letters, Vol. 417, 28.03.2018, p. 131-140.

Research output: Contribution to journalArticle

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