Tanaka Tomohito, Terai Yoshito, Ashihara Keisuke, Fujiwara Satoe, Tanaka Yoshimichi, Sasaki Hiroshi, Tsunetoh Satoshi, Ohmichi Masahide
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Japan.
PLoS One. 2017 May 4;12(5):e0177019. doi: 10.1371/journal.pone.0177019. eCollection 2017.
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.
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.
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.
PD - 0332991，即选择性细胞周期蛋白依赖性激酶4/6抑制剂帕博西尼，通过抑制视网膜母细胞瘤（Rb）蛋白的磷酸化来引起细胞周期停滞。本研究的目的是评估PD - 0332991在子宫内膜癌中的治疗潜力。
用PD - 0332991处理四种人子宫内膜癌细胞系ECC、HEC1A、HEC108和TEN，并评估其功能。在体内，在皮下子宫内膜癌模型中评估治疗效果。对337例子宫内膜癌标本进行免疫组织化学分析。增殖试验显示，表达Rb的4种细胞系中有2种对PD - 0332991敏感，IC50分别为0.65 μM（HEC1A）和0.58 μM（HEC108）。根据流式细胞术，这两种细胞系在用PD - 0332991处理后均出现G0/G1细胞周期停滞。在体内，PD - 0332991具有抗肿瘤作用，可降低Ki67活性和Rb磷酸化水平。免疫组织化学分析显示，Rb的阳性率为67.7%，然而，Rb的表达水平与肿瘤分级之间无显著相关性。
PD - 0332991对表达Rb蛋白的子宫内膜癌细胞系具有治疗潜力。我们的免疫组织化学分析显示，约70%的子宫内膜癌患者可能有使用PD - 0332991的治疗指征。值得注意的是，肿瘤分级对治疗指征没有影响。
