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
August-2016 Volume 36 Issue 2

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
August-2016 Volume 36 Issue 2

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

Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells

  • Authors:
    • Eun Ho Kim
    • Hanna Lee
    • Youn Kyoung Jeong
    • Won-Gyun Jung
  • View Affiliations / Copyright

    Affiliations: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea, Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-Ku, Seoul 139-706, Republic of Korea
  • Pages: 763-770
    |
    Published online on: June 10, 2016
       https://doi.org/10.3892/or.2016.4868
  • 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

Colorectal cancer is one of the most common cancers worldwide. Previous studies suggest that chemoradiotherapy is more effective for the treatment of colorectal cancer than is radiotherapy or chemotherapy alone. To enhance the radiosensitivity of tumor cells, several investigators have used targeted therapeutic agents that act as radiosensitizers. In the present study, we provide a scientific rationale for the clinical application of SU5416, an inhibitor of vascular endothelial growth factor receptor-2, as a radiosensitizer for colorectal cancer. Two human colorectal adenocarcinoma cell lines, HCT116 and HT-29, were treated with SU5416 and radiation alone or radiation followed by SU5416. In vitro tests were performed using colony forming assays, flow cytometric analysis, immunohistochemistry, senescence-associated β-galactosidase, tumor cell motility and invasion assays. The combination of radiation and SU5416 synergistically inhibited cell survival and induced apoptosis through reactive oxygen species, enhanced IR-induced premature senescence, and inhibited DNA repair activity, cell migration and invasion. Collectively, our results favor the use of SU5416 and radiotherapy as a combination therapy for the treatment of colon cancer and it can be combined successfully with a radiation regimen to potentiate its antitumor and antimetastatic activities for future clinical trials.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, et al: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 324:709–715. 1991. View Article : Google Scholar : PubMed/NCBI

2 

Seiwert TY, Salama JK and Vokes EE: The concurrent chemoradiation paradigm - general principles. Nat Clin Pract Oncol. 4:86–100. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Siemann DW, Bibby MC, Dark GG, Dicker AP, Eskens FA, Horsman MR, Marmé D and Lorusso PM: Differentiation and definition of vascular-targeted therapies. Clin Cancer Res. 11:416–420. 2005.PubMed/NCBI

4 

Jubb AM, Pham TQ, Hanby AM, Frantz GD, Peale FV, Wu TD, Koeppen HW and Hillan KJ: Expression of vascular endothelial growth factor, hypoxia inducible factor 1α, and carbonic anhydrase IX in human tumours. J Clin Pathol. 57:504–512. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, et al: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 59:99–106. 1999.PubMed/NCBI

6 

Huber PE, Bischof M, Jenne J, Heiland S, Peschke P, Saffrich R, Gröne HJ, Debus J, Lipson KE and Abdollahi A: Trimodal cancer treatment: Beneficial effects of combined antiangiogenesis, radiation, and chemotherapy. Cancer Res. 65:3643–3655. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Bischof M, Abdollahi A, Gong P, Stoffregen C, Lipson KE, Debus JU, Weber KJ and Huber PE: Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells. Int J Radiat Oncol Biol Phys. 60:1220–1232. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Krystal GW, Honsawek S, Kiewlich D, Liang C, Vasile S, Sun L, McMahon G and Lipson KE: Indolinone tyrosine kinase inhibitors block Kit activation and growth of small cell lung cancer cells. Cancer Res. 61:3660–3668. 2001.PubMed/NCBI

9 

Lu B, Geng L, Musiek A, Tan J, Cao C, Donnelly E, McMahon G, Choy H and Hallahan DE: Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium. Int J Radiat Oncol Biol Phys. 58:844–850. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Kharbanda S, Saleem A, Shafman T, Emoto Y, Taneja N, Rubin E, Weichselbaum R, Woodgett J, Avruch J, Kyriakis J, et al: Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase. J Biol Chem. 270:18871–18874. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Leber MF and Efferth T: Molecular principles of cancer invasion and metastasis (Review). Int J Oncol. 34:881–895. 2009.PubMed/NCBI

12 

Begg AC, Stewart FA and Vens C: Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 11:239–253. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Cherrington JM, Strawn LM and Shawver LK: New paradigms for the treatment of cancer: The role of anti-angiogenesis agents. Adv Cancer Res. 79:1–38. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Wachsberger P, Burd R and Dicker AP: Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: Exploring mechanisms of interaction. Clin Cancer Res. 9:1957–1971. 2003.PubMed/NCBI

15 

Jain RK, Duda DG, Clark JW and Loeffler JS: Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 3:24–40. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Stadler WM, Heimann R, Karczmar GS, Gajewski T, Kindler H, MacEaneny P, Zamora M, Medved M and Vokes E: Clinical evaluation of tumor angiogenesis markers in metastatic cancer. Proc Am Soc Clin Oncol. 20:3822001.

17 

Timke C, Zieher H, Roth A, Hauser K, Lipson KE, Weber KJ, Debus J, Abdollahi A and Huber PE: Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy. Clin Cancer Res. 14:2210–2219. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Bernier J, Hall EJ and Giaccia A: Radiation oncology: A century of achievements. Nat Rev Cancer. 4:737–747. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Brooks PC: Cell adhesion molecules in angiogenesis. Cancer Metastasis Rev. 15:187–194. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Basset P, Okada A, Chenard MP, Kannan R, Stoll I, Anglard P, Bellocq JP and Rio MC: Matrix metalloproteinases as stromal effectors of human carcinoma progression: Therapeutic implications. Matrix Biol. 15:535–541. 1997. View Article : Google Scholar : PubMed/NCBI

21 

Johnsen M, Lund LR, Rømer J, Almholt K and Danø K: Cancer invasion and tissue remodeling: Common themes in proteolytic matrix degradation. Curr Opin Cell Biol. 10:667–671. 1998. View Article : Google Scholar : PubMed/NCBI

22 

Roberts PJ and Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 26:3291–3310. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim EH, Lee H, Jeong YK and Jung W: Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells. Oncol Rep 36: 763-770, 2016.
APA
Kim, E.H., Lee, H., Jeong, Y.K., & Jung, W. (2016). Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells. Oncology Reports, 36, 763-770. https://doi.org/10.3892/or.2016.4868
MLA
Kim, E. H., Lee, H., Jeong, Y. K., Jung, W."Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells". Oncology Reports 36.2 (2016): 763-770.
Chicago
Kim, E. H., Lee, H., Jeong, Y. K., Jung, W."Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells". Oncology Reports 36, no. 2 (2016): 763-770. https://doi.org/10.3892/or.2016.4868
Copy and paste a formatted citation
x
Spandidos Publications style
Kim EH, Lee H, Jeong YK and Jung W: Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells. Oncol Rep 36: 763-770, 2016.
APA
Kim, E.H., Lee, H., Jeong, Y.K., & Jung, W. (2016). Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells. Oncology Reports, 36, 763-770. https://doi.org/10.3892/or.2016.4868
MLA
Kim, E. H., Lee, H., Jeong, Y. K., Jung, W."Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells". Oncology Reports 36.2 (2016): 763-770.
Chicago
Kim, E. H., Lee, H., Jeong, Y. K., Jung, W."Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells". Oncology Reports 36, no. 2 (2016): 763-770. https://doi.org/10.3892/or.2016.4868
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