Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
March-2015 Volume 33 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2015 Volume 33 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells

  • Authors:
    • Hong Ma
    • Jianping Bi
    • Tao Liu
    • Yang Ke
    • Sheng Zhang
    • Tao Zhang
  • View Affiliations / Copyright

    Affiliations: Cancer Center of Wuhan Union Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
  • Pages: 1161-1170
    |
    Published online on: December 30, 2014
       https://doi.org/10.3892/or.2014.3699
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to explore the efficacy and mechanism of the radiosensitisation of icotinib hydrochloride (IH), a novel oral epidermal growth factor receptor-tyrosine kinase activity inhibitor, by evaluating the changes in tumour cell double-strand breaks (DSBs) repair, cell cycle and apoptosis following a combination of IH and radiotherapy (RT) in human colorectal adenocarcinoma cell lines. The HT29 and HCT116 human CRC cell lines were treated with IH and/or radiation. Effects on cell viability and cell cycle progression were measured by MTT, a clonogenic survival assay, and flow cytometry. Immunofluorescent staining and western blot analysis were applied to detect the expression of γ-H2AX and 53BP1 in the different treatment groups. Finally, the in vivo effect on the growth of CRC xenografts was assessed in athymic nude mice. IH inhibited the proliferation and enhanced the radiosensitivity in HT29 and HCT116 CRC cells lines. IH combined with radiation increased cell cycle arrest in the G2/M phase compared to the other treatments in the HT29 cell line (P<0.05). Similarly, cell cycle arrest occurred in the HCT116 cell line, although this increase did not result in significant differences in the RT group (P>0.05). IH combined with radiation significantly inhibited the expression of γ-H2AX and 53BP1 based on results of immunofluorescent staining and western blot analysis. In vivo, IH plus radiation significantly inhibited the tumour growth compared to either agent independently. In conclusion, IH significantly increased the radiosensitivity of HT29 and HCT116 cells in vitro and in vivo. Radiation combined with EGFR blockade inhibited tumour proliferation, increased apoptosis, prolonged G2/M arrest and significantly enhanced DNA injury in colorectal cancer. These data support the clinical trials of biologically targeted and conventional therapies in the treatment of cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Secco GB, Fardelli R, Rovida S, et al: Is intensive follow-up really able to improve prognosis of patients with local recurrence after curative surgery for rectal cancer? Ann Surg Oncol. 7:32–37. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Salo JC, Paty PB, Guillem J, Minsky BD, Harrison LB and Cohen AM: Surgical salvage of recurrent rectal carcinoma after curative resection: a 10-year experience. Ann Surg Oncol. 6:171–177. 1999. View Article : Google Scholar : PubMed/NCBI

3 

Pilipshen SJ, Heilweil M, Quan SH, Sternberg SS and Enker WE: Patterns of pelvic recurrence following definitive resections of rectal cancer. Cancer. 53:1354–1362. 1984. View Article : Google Scholar : PubMed/NCBI

4 

Shin SJ, Yoon HI, Kim NK, et al: Upfront systemic chemotherapy and preoperative short-course radiotherapy with delayed surgery for locally advanced rectal cancer with distant metastases. Radiat Oncol. 6:992011. View Article : Google Scholar : PubMed/NCBI

5 

Bosset JF, Collette L, Calais G, et al: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 355:1114–1123. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Rodel C, Liersch T, Becker H, et al: Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 13:679–687. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Baumann M and Krause M: Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother Oncol. 72:257–266. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Ullrich A and Schlessinger J: Signal transduction by receptors with tyrosine kinase activity. Cell. 61:203–212. 1990. View Article : Google Scholar : PubMed/NCBI

9 

Galizia G, Lieto E, Ferraraccio F, et al: Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann Surg Oncol. 13:823–835. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Porębska I, Harłozińska A and Bojarowski T: Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumour Biol. 21:105–115. 2000. View Article : Google Scholar

11 

Milas L, Mason K, Hunter N, et al: In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 6:701–708. 2000.PubMed/NCBI

12 

Harari PM and Huang SM: Head and neck cancer as a clinical model for molecular targeting of therapy: combining EGFR blockade with radiation. Int J Radiat Oncol Biol Phys. 49:427–433. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Dewdney A, Cunningham D, Tabernero J, et al: Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol. 30:1620–1627. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Shin HK, Kim M-S, Lee JK, et al: Combination effect of cetuximab with radiation in colorectal cancer cells. Tumori. 96:7132010.

15 

Williams KJ, Telfer BA, Stratford IJ and Wedge SR: ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model. Br J Cancer. 86:1157–1161. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Häggblad Sahlberg S1, Spiegelberg D, Lennartsson J, Nygren P, Glimelius B and Stenerlöw B: The effect of a dimeric Affibody molecule (ZEGFR:1907)2 targeting EGFR in combination with radiation in colon cancer cell lines. Int J Oncol. 40:176–184. 2012.

17 

Tan F, Shen X, Wang D, et al: Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung Cancer. 76:177–182. 2012. View Article : Google Scholar

18 

Shi Y, Zhang L, Liu X, et al: Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. The Lancet Oncol. 14:953–961. 2013. View Article : Google Scholar

19 

Santivasi WL and Xia F: Ionizing radiation-induced DNA damage, response, and repair. Antioxid Redox Signal. 21:251–259. 2014. View Article : Google Scholar

20 

Qu YY, Hu SL, Xu XY, et al: Nimotuzumab enhances the radiosensitivity of cancer cells in vitro by inhibiting radiation-induced DNA damage repair. PLoS One. 8:e707272013. View Article : Google Scholar : PubMed/NCBI

21 

Tanaka T, Munshi A, Brooks C, Liu J, Hobbs ML and Meyn RE: Gefitinib radiosensitizes non-small cell lung cancer cells by suppressing cellular DNA repair capacity. Clin Cancer Res. 14:1266–1273. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Herbst RS and Bunn PA Jr: Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clin Cancer Res. 9:5813–5824. 2003.PubMed/NCBI

23 

Dittmann K, Mayer C, Fehrenbacher B, et al: Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem. 280:31182–31189. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Sano D, Kawakami M, Fujita K, et al: Antitumor effects of ZD6474 on head and neck squamous cell carcinoma. Oncol Rep. 17:289–295. 2007.PubMed/NCBI

25 

Rothkamm K and Löbrich M: Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA. 100:5057–5062. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Burma S, Chen BP, Murphy M, Kurimasa A and Chen DJ: ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 276:42462–42467. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Mah LJ, Orlowski C, Ververis K, Vasireddy RS, El-Osta A and Karagiannis TC: Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks. Genome Integr. 2:32011. View Article : Google Scholar

28 

Lobrich M, Shibata A, Beucher A, et al: gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle. 9:662–669. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Ward IM, Difilippantonio S, Minn K, et al: 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice. Mol Cell Biol. 25:10079–10086. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Bouwman P, Aly A, Escandell JM, et al: 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol. 17:688–695. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Nuciforo PG, Luise C, Capra M, Pelosi G and d’Adda di Fagagna F: Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression. Carcinogenesis. 28:2082–2088. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Clarke A, Jones N, Pryde F, Adachi Y and Sansom O: 53BP1 deficiency in intestinal enterocytes does not alter the immediate response to ionizing radiation, but leads to increased nuclear area consistent with polyploidy. Oncogene. 26:6349–6355. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Morales JC, Franco S, Murphy MM, et al: 53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis. Proc Natl Acad Sci USA. 103:3310–3315. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Li X, Xu B, Moran MS, et al: 53BP1 functions as a tumor suppressor in breast cancer via the inhibition of NF-κB through miR-146a. Carcinogenesis. 33:2593–2600. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Park JS, Jun HJ, Cho MJ, et al: Radiosensitivity enhancement by combined treatment of celecoxib and gefitinib on human lung cancer cells. Clin Cancer Res. 12:4989–4999. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma H, Bi J, Liu T, Ke Y, Zhang S and Zhang T: Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells. Oncol Rep 33: 1161-1170, 2015.
APA
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., & Zhang, T. (2015). Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells. Oncology Reports, 33, 1161-1170. https://doi.org/10.3892/or.2014.3699
MLA
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., Zhang, T."Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells". Oncology Reports 33.3 (2015): 1161-1170.
Chicago
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., Zhang, T."Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells". Oncology Reports 33, no. 3 (2015): 1161-1170. https://doi.org/10.3892/or.2014.3699
Copy and paste a formatted citation
x
Spandidos Publications style
Ma H, Bi J, Liu T, Ke Y, Zhang S and Zhang T: Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells. Oncol Rep 33: 1161-1170, 2015.
APA
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., & Zhang, T. (2015). Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells. Oncology Reports, 33, 1161-1170. https://doi.org/10.3892/or.2014.3699
MLA
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., Zhang, T."Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells". Oncology Reports 33.3 (2015): 1161-1170.
Chicago
Ma, H., Bi, J., Liu, T., Ke, Y., Zhang, S., Zhang, T."Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells". Oncology Reports 33, no. 3 (2015): 1161-1170. https://doi.org/10.3892/or.2014.3699
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team