Alteration of DNA damage signaling pathway profile in radiation‑treated glioblastoma stem‑like cells

Sun,Chao; Wang,Zhongyong; Song,Wuchao; Chen,Baomin; Zhang,Jinshi; Dai,Xingliang; Wang,Lin; Wu,Jinding; Lan,Qing; Huang,Qiang; Dong,Jun

doi:10.3892/ol.2015.3411

September-2015 Volume 10 Issue 3

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September-2015 Volume 10 Issue 3

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Article

Alteration of DNA damage signaling pathway profile in radiation‑treated glioblastoma stem‑like cells

Authors:
- Chao Sun
- Zhongyong Wang
- Wuchao Song
- Baomin Chen
- Jinshi Zhang
- Xingliang Dai
- Lin Wang
- Jinding Wu
- Qing Lan
- Qiang Huang
- Jun Dong
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
Pages: 1769-1774
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Published online on: June 22, 2015

https://doi.org/10.3892/ol.2015.3411
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Abstract

The present study aimed to investigate the alteration of the DNA damage signaling pathway profile in radiation‑treated glioblastoma stem‑like cells (GSLCs), and also aimed to explore potential targets for overcoming glioblastoma radioresistance. Serum‑free medium was used to isolate and culture GSLCs. Cell growth was detected using a cell counting kit‑8 assay and cell sorting analysis was performed by flow cytometry. X‑ray irradiation was produced by a Siemens‑Primus linear accelerator. Reverse transcription‑quantitative polymerase chain reaction (qPCR)was performed to investigate target genes. SPSS 15.0 was used for all statistical analyses. Human glioblastoma U251 and U87 cells were cultured in serum‑free medium supplemented with epidermal growth factor and fibroblast growth factor 2, which constitutes tumor sphere medium, and demonstrated sphere formation, with significantly increased the proportion of CD133+ and Nestin+ cells, which are referred to as GSLCs. The present data revealed that treatment with 10 Gy X‑ray radiation alters the expression profile of DNA damage‑associated genes in GSLCs. The expression levels of 12 genes demonstrated a ≥2‑fold increase in the irradiated U87 GSLCs compared with the untreated U87 GSLCs. Three genes, consisting of XPA, RAD50 and PPP1R15A, were selected from the 12 genes by gene functional searching and qPCR confirmatory studies, as these genes were considered to be potential targets for overcoming radioresistance. The expression of XPA, RAD50 and PPP1R15A is significantly increased in U87 and U251 radiation resistant GSLCs, indicating three potential targets for overcoming the radioresistance of GSLCs.

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1	DeAngelis LM: Brain tumors. N Engl J Med. 344:114–123. 2001. View Article : Google Scholar : PubMed/NCBI
2	Stupp R, Mason WP, van den Bent MJ, et al: European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
3	Ravizza R, Cereda E, Monti E and Gariboldi MB: The piperidine nitroxide Tempol potentiates the cytotoxic effects of temozolomide in human glioblastoma cells. Int J Oncol. 25:1817–1822. 2004.PubMed/NCBI
4	Bruyere C, Mijatovic T, Lonez C, et al: Temozolomide-induced modification of the CXC chemokine network in experimental gliomas. Int J Oncol. 38:1453–1464. 2011.PubMed/NCBI
5	Ashizawa T, Akiyama Y, Miyata H, et al: Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line. Int J Oncol. 45:411–418. 2014.PubMed/NCBI
6	Shi L, Zhang S, Feng K, et al: MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis. Int J Oncol. 40:119–129. 2012.PubMed/NCBI
7	Fouse SD, Nakamura JL, James CD, Chang S and Costello JF: Response of primary glioblastoma cells to therapy is patient specific and independent of cancer stem cell phenotype. Neuro Oncol. 16:361–371. 2014. View Article : Google Scholar : PubMed/NCBI
8	Estrada-Bernal A, Palanichamy K, Ray Chaudhury A and Van Brocklyn JR: Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma. Neuro Oncol. 14:405–415. 2012. View Article : Google Scholar : PubMed/NCBI
9	Rich JN: Cancer stem cells in radiation resistance. Cancer Res. 67:8980–8984. 2007. View Article : Google Scholar : PubMed/NCBI
10	Bao S, Wu Q, McLendon RE, et al: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI
11	Wu J, Lai G, Wan F, Xiao Z, Zeng L, et al: Knockdown of checkpoint kinase 1 is associated with the increased radiosensitivity of glioblastoma stem-like cells. Tohoku J Exp Med. 226:267–274. 2012. View Article : Google Scholar : PubMed/NCBI
12	Soeda A, Park M, Lee D, et al: Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene. 28:3949–3959. 2009. View Article : Google Scholar : PubMed/NCBI
13	Christensen K, Aaberg-Jessen C, Andersen C, Goplen D, Bjerkvig R and Kristensen BW: Immunohistochemical expression of stem cell, endothelial cell and chemosensitivity markers in primary glioma spheroids cultured in serum-containing and serum-free medium. Neurosurgery. 66:933–947. 2010. View Article : Google Scholar : PubMed/NCBI
14	Zhang M, Song T, Yang L, et al: Nestin and CD133: Valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res. 27(85)2008.
15	Li Z, Musich PR, Cartwright BM, Wang H and Zou Y: UV-induced nuclear import of XPA is mediated by importin-alpha4 in an ATR-dependent manner. PloS One. 8:e682972013. View Article : Google Scholar : PubMed/NCBI
16	Li Z, Musich PR and Zou Y: Differential DNA damage responses in p53 proficient and deficient cells: Cisplatin-induced nuclear import of XPA is independent of ATR checkpoint in p53-deficient lung cancer cells. Int J Biochem Mol Biol. 2:138–145. 2011.PubMed/NCBI
17	Li Z, Musich PR, Serrano MA, Dong Z and Zou Y: XPA-mediated regulation of global nucleotide excision repair by ATR is p53-dependent and occurs primarily in S-phase. PloS One. 6:e283262011. View Article : Google Scholar : PubMed/NCBI
18	Gatei M, Jakob B, Chen P, et al: ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control. J Biol Chem. 286:31542–31556. 2011. View Article : Google Scholar : PubMed/NCBI
19	Machida K, McNamara G, Cheng KT, et al: Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. J Immunol. 185:6985–6998. 2010. View Article : Google Scholar : PubMed/NCBI
20	Kuroda S, Fujiwara T, Shirakawa Y, et al: Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. Cancer Res. 70:9339–9348. 2010. View Article : Google Scholar : PubMed/NCBI
21	Grishin AV, Azhipa O, Semenov I and Corey SJ: Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. Proc Natl Acad Sci USA. 98:10172–10177. 2001. View Article : Google Scholar : PubMed/NCBI
22	Hollander MC, Zhan Q, Bae I and Fornace AJ Jr: Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. J Biol Chem. 272:13731–13737. 1997. View Article : Google Scholar : PubMed/NCBI
23	Hollander MC, Sheikh MS, Yu K, et al: Activation of Gadd34 by diverse apoptotic signals and suppression of its growth inhibitory effects by apoptotic inhibitors. Int J Cancer. 96:22–31. 2001. View Article : Google Scholar : PubMed/NCBI
24	Adler HT, Chinery R, Wu DY, et al: Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. Mol Cell Biol. 19:7050–7060. 1999.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Alteration of DNA damage signaling pathway profile in radiation‑treated glioblastoma stem‑like cells

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