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Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway

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Tumor Biology

Abstract

The purpose of this study was to evaluate the radiation-enhancing effect of sodium glycididazole, and the corresponding mechanisms of action on laryngeal cancer cells. Two laryngeal cancer cell lines (Hep-2 and UT-SCC-19A) were irradiated with X-rays in the presence or absence of sodium glycididazole. Cell survival, DNA damage and repair, cell apoptosis, cell cycle distribution, expression of proteins related to cell cycle checkpoint, and apoptosis were measured. Significantly increased DNA damages, decreased cells in the G1 phase, arrested cells at G2/M phase, decreased DNA repair protein XRCC1 foci formation, and enhanced cell apoptosis were observed in laryngeal cell lines treated by sodium glycididazole combined with irradiation compared with the irradiation alone. The combined treatment downregulated the protein expressions of ataxia–telangiectasia mutated (ATM), p-ATM, CHK2, and P53 but upregulated the protein expressions of MDM2 and Cdk2. This study indicates that sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway in vitro and in vivo.

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References

  1. Lefebvre JL. Laryngeal preservation in head and neck cancer: multidisciplinary approach. Lancet Oncol. 2006;7(9):747–55.

    Article  PubMed  Google Scholar 

  2. Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, et al. Long-term results of RTOG 91–11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845–52.

    Article  CAS  PubMed  Google Scholar 

  3. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008;26(21):3582–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007;25(26):4066–74.

    Article  PubMed  Google Scholar 

  5. Ke Q, Wu J, Ming B, Zhu S, Yu M, Wang Y, et al. Identification of the PAG1 gene as a novel target of inherent radioresistance in human laryngealcarcinoma cells. Cancer Biother Radiopharm. 2012;27(10):678–84.

    Article  CAS  PubMed  Google Scholar 

  6. Rastogi RP, Richa, Kumar A, Tyagi MB, Sinha RP. Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids. 2010;2010:592980.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Schaue D, McBride WH. Counteracting tumor radioresistance by targeting DNA repair. Mol Cancer Ther. 2005;4(10):1548–50.

    Article  CAS  PubMed  Google Scholar 

  8. Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, et al. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 1999;59(17):4375–82.

    CAS  PubMed  Google Scholar 

  9. Golding SE, Rosenberg E, Khalil A, McEwen A, Holmes M, Neill S, et al. Double strand break repair by homologous recombination is regulated by cell cycle-independent signaling via ATM in human glioma cells. J Biol Chem. 2004;279(15):15402–10.

    Article  CAS  PubMed  Google Scholar 

  10. Lavin MF. ATM activation and DNA damage response. Cell Cycle. 2007;6(8):931–42.

    Article  CAS  PubMed  Google Scholar 

  11. Burma S, Chen BP, Murphy M, Kurimasa A. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 2001;276(45):42462–7.

    Article  CAS  PubMed  Google Scholar 

  12. Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids 2010 2010.

  13. Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development andtumorigenesis. Oncogene. 1999;18(55):7883–99.

    Article  CAS  PubMed  Google Scholar 

  14. Toulany M, Mihatsch J, Holler M, Chaachouay H, Rodemann HP. Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is stimulated by ATM inhibition. Radiother Oncol. 2014;111(2):228–36.

    Article  CAS  PubMed  Google Scholar 

  15. Guo X, Yang C, Qian X, Lei T, Li Y, Shen H, et al. Estrogen receptor α regulates ATM Expression through miRNAs in breast cancer. Clin Cancer Res. 2013;19(18):4994–5002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hennig J, McShane MP, Cordes N, Eke I. APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM. Cell Death Dis. 2014;5:e1199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ma CQ, Yang Y, Wang JM, Du GS, Shen Q, Liu Y, et al. The aPKCι blocking agent ATM negatively regulates EMT and invasion of hepatocellular carcinoma. Cell Death Dis. 2014;5:e1129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zeng YC, Wu R, Xu ZG, Zhang XY, Fan GL, Wu LN, et al. Safety and radiation-enhancing effect of sodium glycididazole in locoregionally advanced laryngeal cancers previously treated with platinum-containing chemotherapy regimens: a preliminary report. Cancer Radiother. 2010;14(1):59–64.

    Article  CAS  PubMed  Google Scholar 

  19. Fu LQ, Huang F, Guo JH, Gao HZ, Liang YQ, Li J, et al. Phase I clinical pharmacokinetics of glycididazolum natrium. Chin J Pharmacol Toxicol. 2004;18:87–92.

    CAS  Google Scholar 

  20. Cai L, Liu MZ, Gu MF, Liu H, Chen EC, Hu YH, et al. Phase I study of CM-Na combined with concurrent radiochemotherapy for advanced esophageal carcinoma. Ai Zheng. 2005;24(5):582–6.

    PubMed  Google Scholar 

  21. Yang J, Liu MZ, Cai L, Hu YH, Liu H, Li QQ, et al. Phase II clinical trial of sodium glyci-didazole (CM-Na) combined with concurrent radiochemotherapy for advanced esophageal carcinoma. Ai Zheng. 2008;27(6):622–6.

    PubMed  Google Scholar 

  22. Sugie C, Shibamoto Y, Ito M, Ogino H, Suzuki H, Uto Y, et al. Reevaluation of the radiosensitizing effects of sanazole and nimorazole in vitro and in vivo. J Radiat Res. 2005;46(4):453–9.

    Article  CAS  PubMed  Google Scholar 

  23. Tichý A, Vávrová J, Pejchal J, Rezácová M. Ataxia-telangiectasia mutated kinase (ATM) as a central regulator of radiation-induced DNA damage response. Acta Med (Hradec Kralove). 2010;53(1):13–7.

    Article  Google Scholar 

  24. Zheng X, Gao J, Zhang H, Zhang H, Zhu Q, Meng X, et al. Radiosensitizing efficiency of sodium glycididazole on v(79) cells in vitro. J Radiat Res Radiat Proc. 1995;3:213–8.

    Google Scholar 

  25. Zhang Q, Zhang C, He J, Guo Q, Hu D, Yang X, et al. STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma. Tumour Biol. 2015;36(3):2135–42.

    Article  CAS  PubMed  Google Scholar 

  26. Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201–21.

    Article  CAS  PubMed  Google Scholar 

  27. Kim WJ, Vo QN, Shrivastav M, Lataxes TA, Brown KD. Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene. 2002;21(24):3864–71.

    Article  CAS  PubMed  Google Scholar 

  28. Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73–112.

    Article  CAS  PubMed  Google Scholar 

  29. Ferguson DO, Sekiguchi JM, Frank KM, Gao Y, Sharpless NE, Gu Y, et al. The interplay between nonhomologous end-joining and cell cycle checkpoint factors indevelopment, genomic stability, and tumorigenesis. Cold Spring Harb Symp Quant Biol. 2000;65:395–403.

    Article  CAS  PubMed  Google Scholar 

  30. Stucki M, Stagljar I, Jónsson ZO, Hübscher U. A coordinated interplay: proteins with multiple functions in DNA replication, DNA repair, cell cycle/checkpoint control, and transcription. Prog Nucleic Acid Res Mol Biol. 2001;65:261–98.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81201803) and by a grant from Luye Pharma Group Ltd. (Shanghai, China).

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Authors and Affiliations

  1. Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China

    Yue-Can Zeng, Rui Xing, Feng Chi, Qiong-Yu Duan, Yu-Nan Sun, Nan Niu & Rong Wu

  2. Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA

    Jing Zeng

  3. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China

    Ming Xue

  4. Cancer Institute, No.1 Hospital of China Medical University, Shenyang, 110001, China

    Yan Xin

  5. Department of Otorhinolaryngology, Harbin First Hospital, 151, Diduan Street, Harbin, 150010, China

    Guo-Liang Fan

  6. Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, China

    Hong-Mei Wang

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  1. Yue-Can Zeng
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  2. Rui Xing
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Correspondence to Rong Wu.

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Zeng, YC., Xing, R., Zeng, J. et al. Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway. Tumor Biol. 37, 5869–5878 (2016). https://doi.org/10.1007/s13277-015-4278-1

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  • DOI: https://doi.org/10.1007/s13277-015-4278-1

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