title: Radiosensitization in esophageal squamous cell carcinoma: Effect of polo-like kinase 1 inhibition.
abstract: OBJECTIVE
  This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib.
  
  
  METHODS
  Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models.
  
  
  RESULTS
  Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone.
  
  
  CONCLUSIONS
  The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.|Department of Radiation Oncology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.|Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
authors.forename: Jenny Ling-Yu
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.|Department of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
authors.forename: Jo-Pai
authors.initials: JP
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan. yusen0814@gmail.com.|Department of Medical Imaging, National Taiwan University Hospital, No.7, Chung-Shan South Road, 100, Taipei, Taiwan. yusen0814@gmail.com.|Department of Medical Imaging, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. yusen0814@gmail.com.
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuan-Chun
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Jaw
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.|Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan.
authors.forename: Jason Chia-Hsien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.|Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.|Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000532:radiotherapy*; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011621:Pteridines / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents; D014410:Tumor Stem Cell Assay; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D011838:Radiation-Sensitizing Agents; D000097869:Polo-Like Kinase 1; C541363:BI 6727
keywords: Apoptosis; Drug screening assays, antitumor; Radiation therapy; Radiation tolerance; Volasertib