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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2014

Open Access 01-12-2014 | Research

Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of homologous recombination repair

Authors: Qin Qin, Hongyan Cheng, Jing Lu, Liangliang Zhan, Jianchao Zheng, Jing Cai, Xi Yang, Liping Xu, Hongcheng Zhu, Chi Zhang, Jia Liu, Jianxin Ma, Xizhi Zhang, Shengbin Dai, Xinchen Sun

Published in: Journal of Hematology & Oncology | Issue 1/2014

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Abstract

Background

Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC).

Methods

Cell viability was determined by CCK8 assay. The radiosensitization effect of YM155 was evaluated by clonogenic survival and progression of tumor xenograft. Cell cycle progression was determined by flow cytometric analysis. Radiation-induced DNA double strand break (DSB) and homologous recombination repair (HRR) were detected by the staining of γ-H2AX and RAD51, respectively. Expression of survivin and cell cycle regulators was detected by Western blot analysis.

Results

YM155 induced radiosensitization in ESCC cell lines Eca109 and TE13, associated with the abrogation of radiation induced G2/M checkpoint, impaired Rad51 focus formation, and the prolongation of γ-H2AX signaling. G2/M transition markers, including the activation of cyclinB1/Cdc2 kinase and the suppression of Cdc2 Thr14/Tyr15 phosphorylation were induced by YM155 in irradiated cells. The combination of YM155 plus irradiation delayed the growth of ESCC tumor xenografts to a greater extent compared with either treatment modality alone.

Conclusions

Our findings suggest that the abrogation of G2 checkpoint and the inhibition of HRR contribute to radiosensitization by YM155 in ESCC cells.
Appendix
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Metadata
Title
Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of homologous recombination repair
Authors
Qin Qin
Hongyan Cheng
Jing Lu
Liangliang Zhan
Jianchao Zheng
Jing Cai
Xi Yang
Liping Xu
Hongcheng Zhu
Chi Zhang
Jia Liu
Jianxin Ma
Xizhi Zhang
Shengbin Dai
Xinchen Sun
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-014-0062-8

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