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07.03.2016 | Original Article

Radiosensitization in esophageal squamous cell carcinoma

Effect of polo-like kinase 1 inhibition

verfasst von: Jenny Ling-Yu Chen, M.D., Jo-Pai Chen, M.D., Yu-Sen Huang, M.D., Yuan-Chun Tsai, B.S., Ming-Hsien Tsai, M.S., Fu-Shan Jaw, Ph.D., Jason Chia-Hsien Cheng, M.D., Ph.D., Sung-Hsin Kuo, M.D., Ph.D., Ming-Jium Shieh, M.D., Ph.D.

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 4/2016

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Abstract

Purpose

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.

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.

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Titel: Radiosensitization in esophageal squamous cell carcinoma
Effect of polo-like kinase 1 inhibition
verfasst von: Jenny Ling-Yu Chen, M.D.
Jo-Pai Chen, M.D.
Yu-Sen Huang, M.D.
Yuan-Chun Tsai, B.S.
Ming-Hsien Tsai, M.S.
Fu-Shan Jaw, Ph.D.
Jason Chia-Hsien Cheng, M.D., Ph.D.
Sung-Hsin Kuo, M.D., Ph.D.
Ming-Jium Shieh, M.D., Ph.D.
Publikationsdatum: 07.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 4/2016
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-016-0951-6

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Radiosensitization in esophageal squamous cell carcinoma

Effect of polo-like kinase 1 inhibition