Skip to main content
Top
Published in: Tumor Biology 5/2016

01-05-2016 | Original Article

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

Authors: 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

Published in: Tumor Biology | Issue 5/2016

Login to get access

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.
Literature
1.
go back to reference Lefebvre JL. Laryngeal preservation in head and neck cancer: multidisciplinary approach. Lancet Oncol. 2006;7(9):747–55.CrossRefPubMed Lefebvre JL. Laryngeal preservation in head and neck cancer: multidisciplinary approach. Lancet Oncol. 2006;7(9):747–55.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
4.
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
7.
go back to reference Schaue D, McBride WH. Counteracting tumor radioresistance by targeting DNA repair. Mol Cancer Ther. 2005;4(10):1548–50.CrossRefPubMed Schaue D, McBride WH. Counteracting tumor radioresistance by targeting DNA repair. Mol Cancer Ther. 2005;4(10):1548–50.CrossRefPubMed
8.
go back to reference 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.PubMed 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.PubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids 2010 2010. Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids 2010 2010.
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
17.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference 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. 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.
20.
go back to reference 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 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
21.
go back to reference 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 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
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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. 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.
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201–21.CrossRefPubMed Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201–21.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway
Authors
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
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4278-1

Other articles of this Issue 5/2016

Tumor Biology 5/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine