The efficacy of the cyclin-dependent kinase 4-6 inhibitor in endometrial cancerReportar como inadecuado




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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.



Autor: Tomohito Tanaka , Yoshito Terai, Keisuke Ashihara, Satoe Fujiwara, Yoshimichi Tanaka, Hiroshi Sasaki, Satoshi Tsunetoh, Masahide

Fuente: http://plos.srce.hr/



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