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Radiosensitization in esophageal squamous cell carcinoma: Effect of polo-like kinase 1 inhibition.
Strahlenther Onkol ; 192(4): 260-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26952039


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 AND MATERIALS 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.


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.


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.





Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Pteridinas / Radiossensibilizantes / Neoplasias Esofágicas / Carcinoma de Células Escamosas / Sobrevivência Celular / Proteínas Proto-Oncogênicas / Proteínas Serina-Treonina Quinases / Proteínas de Ciclo Celular Limite: Animais / Humanos / Masculino Idioma: Inglês Revista: Strahlenther Onkol Assunto da revista: Neoplasias / Radioterapia Ano de publicação: 2016 Tipo de documento: Artigo País de afiliação: Taiwan