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

• Published in: Cancer gene therapy Vol. 21; no. 3; pp. 103 - 109
• Main Authors: Chu, S-H, Zhou, Z-M, Karri, S, Li, Z-Q, Zhao, J-M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2014; Nature Publishing Group
• Subjects: 631/61/201; 631/67/1059/485; 631/67/1922; Animals; Antitumor agents; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; Biomedical and Life Sciences; Biomedicine; Brain tumors; Cancer; Care and treatment; Carrier proteins; Cell Line, Tumor; DNA Damage; DNA methylation; DNA nucleotidylexotransferase; DNA Repair; Drug metabolism; Gene Expression; Gene Therapy; Genetic aspects; Genetic research; Glioma; Glioma - genetics; Glioma - metabolism; Glioma - radiotherapy; Glioma cells; Humans; Identification and classification; Mice; Mice, Inbred BALB C; Mice, Nude; Organic Cation Transport Proteins - biosynthesis; Organic Cation Transport Proteins - genetics; Organic cation transporter; original-article; Radiation; Radiation Tolerance; Radiosensitivity; Radiosensitization; Up-Regulation; glioma; SLC22A18; irradiation; radiosensitization
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/cgt.2014.4

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.