論文 - 詳細
| RRC ID | 65932 |
|---|---|
| 著者 | Tanaka T, Terai Y, Ashihara K, Fujiwara S, Tanaka Y, Sasaki H, Tsunetoh S, Ohmichi M. |
| タイトル | The efficacy of the cyclin-dependent kinase 4/6 inhibitor in endometrial cancer. |
| ジャーナル | PLoS One |
| 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. 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. 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. |
| 巻・号 | 12(5) |
| ページ | e0177019 |
| 公開日 | 2017-1-1 |
| DOI | 10.1371/journal.pone.0177019 |
| PII | PONE-D-16-45565 |
| PMID | 28472136 |
| PMC | PMC5417643 |
| MeSH | Animals Cell Cycle / drug effects Cell Line, Tumor Cyclin-Dependent Kinase 4 / antagonists & inhibitors* Cyclin-Dependent Kinase 6 / antagonists & inhibitors* Endometrial Neoplasms / enzymology* Endometrial Neoplasms / pathology Female Humans Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Piperazines / pharmacology Protein Kinase Inhibitors / pharmacology* Pyridines / pharmacology Retinoblastoma Protein / metabolism |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | TEN(RCB1433) |