Advertisement

Tumor Biology

, Volume 37, Issue 5, pp 5869–5878 | Cite as

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

  • Yue-Can Zeng
  • Rui Xing
  • Jing Zeng
  • Ming Xue
  • Feng Chi
  • Yan Xin
  • Guo-Liang Fan
  • Hong-Mei Wang
  • Qiong-Yu Duan
  • Yu-Nan Sun
  • Nan Niu
  • Rong Wu
Original Article

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.

Keywords

Sodium glycididazole Laryngeal cancer Radiation-enhancing effect ATM signaling pathway 

Notes

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).

Compliance with ethical standard

Conflicts of interest

None

References

  1. 1.
    Lefebvre JL. Laryngeal preservation in head and neck cancer: multidisciplinary approach. Lancet Oncol. 2006;7(9):747–55.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007;25(26):4066–74.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Schaue D, McBride WH. Counteracting tumor radioresistance by targeting DNA repair. Mol Cancer Ther. 2005;4(10):1548–50.CrossRefPubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 10.
    Lavin MF. ATM activation and DNA damage response. Cell Cycle. 2007;6(8):931–42.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 12.
    Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids 2010 2010.Google Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.Google Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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. 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.CrossRefPubMedGoogle Scholar
  26. 26.
    Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201–21.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yue-Can Zeng
    • 1
  • Rui Xing
    • 1
  • Jing Zeng
    • 2
  • Ming Xue
    • 3
  • Feng Chi
    • 1
  • Yan Xin
    • 4
  • Guo-Liang Fan
    • 5
  • Hong-Mei Wang
    • 6
  • Qiong-Yu Duan
    • 1
  • Yu-Nan Sun
    • 1
  • Nan Niu
    • 1
  • Rong Wu
    • 1
  1. 1.Department of Medical Oncology, Cancer CenterShengjing Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Radiation OncologyUniversity of Washington School of MedicineSeattleUSA
  3. 3.Department of Obstetrics and GynecologyShengjing Hospital of China Medical UniversityShenyangChina
  4. 4.Cancer InstituteNo.1 Hospital of China Medical UniversityShenyangChina
  5. 5.Department of OtorhinolaryngologyHarbin First HospitalHarbinChina
  6. 6.Department of Radiation OncologyNanfang Hospital of Southern Medical UniversityGuangzhouChina

Personalised recommendations