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
December-2014 Volume 32 Issue 6

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
December-2014 Volume 32 Issue 6

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

The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells

  • Authors:
    • Eun Ho Kim
    • Mi-Sook Kim
    • Won-Gyun Jung
  • View Affiliations / Copyright

    Affiliations: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea
  • Pages: 2421-2428
    |
    Published online on: September 18, 2014
       https://doi.org/10.3892/or.2014.3497
  • 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 malignancies in the world, and is generally treated more effectively by chemoradiotherapy rather than radiotherapy or chemotherapy alone. Targeted radiosensitizers are often used in order to enhance the radiosensitivity of tumor cells. The aim of the present study was to identify the mechanism of radiosensitization by sorafenib in colorectal cancer. Three human colorectal adenocarcinoma cell lines (HCT116, HT29 and SW480) were treated with sorafenib alone or radiation followed by sorafenib. In vitro tests were performed using colony forming assays, FACS analysis, immunohistochemistry, tumor cell motility assays, invasion assays and endothelial tube formation assays. Sorafenib enhanced the anti-proliferative effects of radiation, reducing colony formation, increasing G2/M arrest and enhancing radiation-induced apoptosis by reactive oxygen species. Sorafenib also inhibited the repair of radiation-induced DNA damage by blocking the activation of DNA-dependent protein kinase. Combination treatment significantly inhibited tumor cell migration, tumor cell invasion and vascular endothelial growth factor-mediated angiogenesis in vitro. Taken together, our results provide a scientific rationale for the use of sorafenib with radiotherapy in colon cancer and suggest a clinical utility for this approach.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar

2 

Saltz LB and Minsky B: Adjuvant therapy of cancers of the colon and rectum. Surg Clin North Am. 82:1035–1058. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Krook JE, Moertel CG, Gunderson LL, 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

4 

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

5 

Wilhelm SM, Carter C, Tang L, et al: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM and Lynch M: Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 7:3129–3140. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Iyer R, Fetterly G, Lugade A and Thanavala Y: Sorafenib: a clinical and pharmacologic review. Expert Opin Pharmacother. 11:1943–1955. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Siegel AB, Olsen SK, Magun A and Brown RS Jr: Sorafenib: where do we go from here? Hepatology. 52:360–369. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Escudier BET, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R and Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. New Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Gupta-Abramson V, Troxel AB, Nellore A, et al: Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 26:4714–4719. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Takimoto CH and Awada A: Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. Cancer Chemother Pharmacol. 61:535–548. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Kumar P, Benedict R, Urzua F, Fischbach C, Mooney D and Polverini P: Combination treatment significantly enhances the efficacy of antitumor therapy by preferentially targeting angiogenesis. Lab Invest. 85:756–767. 2005. View Article : Google Scholar

13 

Plastaras JP, Kim SH, Liu YY, et al: Cell cycle-dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. 67:9443–9454. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Dal Lago L, D’Hondt V and Awada A: Selected combination therapy with sorafenib: a review of clinical data and perspectives in advanced solid tumors. Oncologist. 13:845–858. 2008.PubMed/NCBI

15 

Azad N, Annunziata C, Barrett T, et al: Dual targeting of vascular endothelial growth factor (VEGF) with sorafenib and bevacizumab: clinical and translational results. J Clin Oncol (Meeting abstracts). 25:35422007.

16 

Kasibhatla M, Steinberg P, Meyer J, Ernstoff MS and George DJ: Radiation therapy and sorafenib: clinical data and rationale for the combination in metastatic renal cell carcinoma. Clin Genitourin Cancer. 5:291–294. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Horgan AM, Dawson LA, Swaminath A and Knox JJ: Sorafenib and radiation therapy for the treatment of advanced hepatocellular carcinoma. J Gastrointest Cancer. 43:344–348. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Jeong YK, Kim MS, Lee JY, et al: Sorafenib acts synergistically in combination with radiotherapy without causing intestinal damage in colorectal cancer. Tumori. 99:176–182. 2013.PubMed/NCBI

19 

Jackson SP: Sensing and repairing DNA double-strand breaks. Carcinogenesis. 23:687–696. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Rogakou EP, Pilch DR, Orr AH, Ivanova VS and Bonner WM: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 273:5858–5868. 1998. View Article : Google Scholar : PubMed/NCBI

21 

Bonner WM, Redon CE, Dickey JS, et al: GammaH2AX and cancer. Nat Rev Cancer. 8:957–967. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Bourton EC, Plowman PN, Smith D, Arlett CF and Parris CN: Prolonged expression of the γ-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment. Int J Cancer. 129:2928–2934. 2011.

23 

Collis SJ, DeWeese TL, Jeggo PA and Parker AR: The life and death of DNA-PK. Oncogene. 24:949–961. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Smith GC and Jackson SP: The DNA-dependent protein kinase. Genes Dev. 13:916–934. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Douglas P, Sapkota G, Morrice N, et al: Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem J. 368:243–251. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Pignochino Y, Grignani G, Cavalloni G, et al: Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer. 8:1182009. View Article : Google Scholar

27 

Basset P, Okada A, Chenard MP, et al: Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. Matrix Biol. 15:535–541. 1997. View Article : Google Scholar : PubMed/NCBI

28 

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

29 

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, Kim M and Jung W: The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells. Oncol Rep 32: 2421-2428, 2014.
APA
Kim, E.H., Kim, M., & Jung, W. (2014). The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells. Oncology Reports, 32, 2421-2428. https://doi.org/10.3892/or.2014.3497
MLA
Kim, E. H., Kim, M., Jung, W."The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells". Oncology Reports 32.6 (2014): 2421-2428.
Chicago
Kim, E. H., Kim, M., Jung, W."The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells". Oncology Reports 32, no. 6 (2014): 2421-2428. https://doi.org/10.3892/or.2014.3497
Copy and paste a formatted citation
x
Spandidos Publications style
Kim EH, Kim M and Jung W: The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells. Oncol Rep 32: 2421-2428, 2014.
APA
Kim, E.H., Kim, M., & Jung, W. (2014). The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells. Oncology Reports, 32, 2421-2428. https://doi.org/10.3892/or.2014.3497
MLA
Kim, E. H., Kim, M., Jung, W."The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells". Oncology Reports 32.6 (2014): 2421-2428.
Chicago
Kim, E. H., Kim, M., Jung, W."The mechanisms responsible for the radiosensitizing effects of sorafenib on colon cancer cells". Oncology Reports 32, no. 6 (2014): 2421-2428. https://doi.org/10.3892/or.2014.3497
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