title: Carfilzomib induces G2/M cell cycle arrest in human endometrial cancer cells via upregulation of p21Waf1/Cip1and p27Kip1.
abstract: OBJECTIVE
  Carfilzomib is a second-generation tetrapeptide epoxyketone proteasome inhibitor used in current clinical therapy of hematologic malignancies. The mechanism of proteasome inhibition in endometrial cancer is not very clear. Carfilzomib inhibition of type I endometrial carcinoma cell proliferation by inducing cell cycle arrest at the G2/M phase was investigated in our study.
  
  
  METHODS
  HEC-1-A and Ishikawa endometrial carcinoma cell lines and three tumor cell lines were treated by different concentrations of carfilzomib. Methyl thiazolyl tetrazolium (MTT) assay was used to detect cell viability. Flow cytometry was used to analyze the cell cycle. Western blot was used to detect proteins involved in cell cycle progression.
  
  
  RESULTS
  Carfilzomib impaired viability of myelogenous leukemia cell line K562, cervical cancer cell line HeLa, hepatocellular carcinoma cell line SMCC-7721, and endometrial carcinoma cell lines HEC-1-A and Ishikawa. The cell cycle was arrested at the G2/M phase in carfilzomib-treated HEC-1-A endometrial carcinoma cells, while it was arrested at both S and G2/M phases in carfilzomib-treated Ishikawa cells. Carfilzomib treatment significantly induced p21Waf1/ Cip1and p27, while substantially reduced cyclin D3 and cyclin-dependent kinase 1.
  
  
  CONCLUSIONS
  This study showed that carfilzomib inhibited endometrial cancer proliferation by upregulating cyclin-dependent kinase inhibitors p21Waf1/Cip1and p27Kip1, and reducing cyclin-dependent kinase 1 to arrest the cell cycle at the G2/M phase.
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhen
authors.affiliation: Geriatric Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, China. Electronic address: luowj@xjtu.edu.cn.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Luo
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D009842:Oligopeptides / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D009842:Oligopeptides; D050760:Cyclin-Dependent Kinase Inhibitor p27; C524865:carfilzomib
keywords: carfilzomib; cell cycle; endometrial carcinoma