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In vitro and in vivo radiosensitization of human glioma U251 cells induced by upregulated expression of SLC22A18

Cancer Gene Therapy volume 21, pages 103–109 (2014)Cite this article

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Abstract

Our previous study showed that solute carrier family 22 (organic cation transporter) member 18 (SLC22A18) downregulation via promoter methylation was associated with the development and progression of glioma, and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea. In this study, we investigated the possible upregulated expression of SLC22A18-induced enhancement of radiosensitivity of human glioma U251 cells in order to provide evidence in support of further clinical investigations. Stably overexpressing SLC22A18 human glioma U251 cells were generated to investigate the effect of SLC22A18 on the sensitivity of cells to irradiation in vitro using clonogenic survival assay. The apoptosis of U251 cells was examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. DNA damage and repair were measured using γH2AX foci. The effect of SLC22A18 on the in vivo tumor radiosensitivity was investigated in the orthotopic mice model. Upregulated expression of SLC22A18 enhanced the radiosensitivity of glioma U251 cells and also enhanced irradiation-induced apoptosis of U251 cells, but irradiation-induced apoptosis did not correlate with radiosensitizing effect of upregulated expression of SLC22A18. The repair of irradiation-induced double-strand-breaks was retarded in stably overexpressing SLC22A18 U251 cells. In the orthotopic mice model, the upregulated expression of SLC22A18 in U251 cells enhanced the effect of irradiation treatment and increased the survival time of mice. These results show that upregulated expression of SLC22A18 radiosensitizes human glioma U251 cells by suppressing DNA repair capacity.

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Abbreviations

SLC22A18:

solute carrier family 22 (organic cation transporter) member 18

PBS:

phosphate-buffered saline.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (30901535), Innovation Program of Shanghai Municipal Education Commission (12YZ046), Research Fund of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (10XJ22010) and the New One Hundred Person Project of Shanghai Jiao Tong University of School of Medicine (10XBR01). We would like to thank Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital of Wuhan University for providing help.

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  1. S-H Chu and Z-M Zhou: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    S-H Chu

  2. Department of Neurosurgery, Dujiangyan Medical Center, Chengdu, China

    Z-M Zhou

  3. Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    S Karri

  4. Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China

    Z-Q Li

  5. Department of Radiology, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    J-M Zhao

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  1. S-H Chu
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Correspondence to S-H Chu or J-M Zhao.

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Chu, SH., Zhou, ZM., Karri, S. et al. In vitro and in vivo radiosensitization of human glioma U251 cells induced by upregulated expression of SLC22A18. Cancer Gene Ther 21, 103–109 (2014). https://doi.org/10.1038/cgt.2014.4

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