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The efficacy of the cyclin-dependent kinase 4/6 inhibitor in endometrial cancer.
- Source :
-
PloS one [PLoS One] 2017 May 04; Vol. 12 (5), pp. e0177019. Date of Electronic Publication: 2017 May 04 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Background: PD-0332991, the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, causes cell cycle arrest by inhibiting phosphorylation of retinoblastoma (Rb) protein. The aim of this study was to evaluate the therapeutic potential of PD-0332991 in endometrial cancer.<br />Methods and Findings: Four human endometrial cancer cell lines, ECC, HEC1A, HEC108 and TEN, were treated with PD-0332991 and their function was evaluated. In vivo, the therapeutic efficacy was evaluated in a model of subcutaneous endometrial cancer. An immunohistochemical analysis was performed in 337 endometrial cancer specimens. A proliferation assay revealed that 2 of the 4 cell lines that expressed Rb were sensitive to PD-0332991 with an IC50 of 0.65 μM (HEC1A) and 0.58 μM (HEC108), respectively. Both cell lines had G0/G1 cell cycle arrest after treatment with PD-0332991 according to flow cytometry. In vivo, PD-0332991 had antitumoral efficacy with a reduction in the activity of Ki67 and phosphorylation of Rb. Immunohistochemical analyses revealed that the positive rate of Rb was 67.7%, however, there was no significant relationship between the expression levels of Rb and the tumor grade.<br />Conclusions: PD-0332991 had therapeutic potential against endometrial cancer cell lines expressing Rb protein. Our immunohistochemical analysis revealed that approximately 70% of patients with endometrial cancer might have therapeutic indications for PD-0332991. Of note, the tumor grade had no impact on the indications for treatment.
- Subjects :
- Animals
Cell Cycle drug effects
Cell Line, Tumor
Endometrial Neoplasms pathology
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Piperazines pharmacology
Pyridines pharmacology
Retinoblastoma Protein metabolism
Cyclin-Dependent Kinase 4 antagonists & inhibitors
Cyclin-Dependent Kinase 6 antagonists & inhibitors
Endometrial Neoplasms enzymology
Protein Kinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28472136
- Full Text :
- https://doi.org/10.1371/journal.pone.0177019