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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
December-2016 Volume 12 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-2016 Volume 12 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

Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment

  • Authors:
    • Yu‑Qiong Ding
    • Qin Qin
    • Yan Yang
    • Xin‑Chen Sun
    • Xi Yang
    • Hong‑Cheng Zhu
    • Xiao‑Chen Chen
    • Hao Zhang
    • Yue‑Hua Yang
    • Lei Gao
    • Ju‑Dong Luo
    • Xi‑Fa Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy, Changzhou Cancer Hospital of Soochow University, Changzhou, Jiangsu 213001, P.R. China, Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
  • Pages: 4671-4676
    |
    Published online on: October 13, 2016
       https://doi.org/10.3892/ol.2016.5247
  • 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

Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation. Sunitinib potently inhibited ESCC cell proliferation in an MTT assay. In a clonogenic survival assay, sunitinib sensitized hypoxic ESCC cells to radiation, with sensitizing enhancement ratios of 1.31‑1.59. In addition, sunitinib promoted the apoptosis of ESCC cells, but did not alter their cell cycle distribution. Radiosensitization was accompanied by inhibition of the radiation‑induced upregulation of hypoxia‑inducible factor (HIF)‑1α and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF‑1α and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Shridhar R, Almhanna K, Meredith KL, Biagioli MC, Chuong MD, Cruz A and Hoffe SE: Radiation therapy and esophageal cancer. Cancer Control. 20:97–110. 2013.PubMed/NCBI

3 

Li S, Jiang S, Jiang W, Zhou Y, Shen XY, Luo T, Kong LP and Wang HQ: Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells. Oncol Lett. 9:1254–1260. 2015.PubMed/NCBI

4 

Williams KJ, Telfer BA, Xenaki D, Sheridan MR, Desbaillets I, Peters HJ, Honess D, Harris AL, Dachs GU, van der Kogel A and Stratford IJ: Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1. Radiother Oncol. 75:89–98. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Hsiao HT, Xing L, Deng X, Sun X, Ling CC and Li GC: Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal cancer cells. Oncol Rep. 32:723–729. 2014.PubMed/NCBI

6 

Semenza GL: Hypoxia-inducible factors: Mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci. 33:207–214. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A, Shinomiya K, Zeng L, Ou G, Zhu Y, Yoshimura M, et al: Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels. Nat Commun. 3:7832012. View Article : Google Scholar : PubMed/NCBI

8 

Sohda M, Ishikawa H, Masuda N, Kato H, Miyazaki T, Nakajima M, Fukuchi M, Manda R, Fukai Y, Sakurai H and Kuwano H: Pretreatment evaluation of combined HIF-1alpha, p53 and p21 expression is a useful and sensitive indicator of response to radiation and chemotherapy in esophageal cancer. Int J Cancer. 110:838–844. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Moon SY, Chang HW, Roh JL, Kim GC, Choi SH, Lee SW, Cho KJ, Nam SY and Kim SY: Using YC-1 to overcome the radioresistance of hypoxic cancer cells. Oral Oncol. 45:915–919. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Staab A, Fleischer M, Loeffler J, Said HM, Katzer A, Plathow C, Einsele H, Flentje M and Vordermark D: Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro. Strahlenther Onkol. 187:252–259. 2011. View Article : Google Scholar : PubMed/NCBI

11 

El Kaffas A, Al-Mahrouki A, Tran WT, Giles A and Czarnota GJ: Sunitinib effects on the radiation response of endothelial and breast tumor cells. Microvasc Res. 92:1–9. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Cuneo KC, Geng L, Fu A, Orton D, Hallahan DE and Chakravarthy AB: SU11248 (sunitinib) sensitizes pancreatic cancer to the cytotoxic effects of ionizing radiation. Int J Radiat Oncol Biol Phys. 71:873–879. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Sun J, Sun Q, Brown MF, Dudgeon C, Chandler J, Xu X, Shu Y, Zhang L and Yu J: The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA. PloS One. 7:e431582012. View Article : Google Scholar : PubMed/NCBI

14 

Matsumoto S, Batra S, Saito K, Yasui H, Choudhuri R, Gadisetti C, Subramanian S, Devasahayam N, Munasinghe JP, Mitchell JB and Krishna MC: Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia. Cancer Res. 71:6350–6359. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Chen G, Xu X, Zhang L, Fu Y, Wang M, Gu H and Xie X: Blocking autocrine VEGF signaling by sunitinib, an anti-cancer drug, promotes embryonic stem cell self-renewal and somatic cell reprogramming. Cell Res. 24:1121–1136. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Shin HW, Cho CH, Kim TY and Park JW: Sunitinib deregulates tumor adaptation to hypoxia by inhibiting HIF-1alpha synthesis in HT-29 colon cancer cells. Biochem Biophys Res Commun. 398:205–211. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA and Kelsen DP: INT 0123 (Radiation Therapy Oncology Group 94–05) phase III trial of combined-modality therapy for esophageal cancer: High-dose versus standard-dose radiation therapy. J Clin Oncol. 20:1167–1174. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Yoshimura M, Itasaka S, Harada H and Hiraoka M: Microenvironment and radiation therapy. Biomed Res Int. 2013:6853082013. View Article : Google Scholar : PubMed/NCBI

19 

Kim DW, Huamani J, Fu A and Hallahan DE: Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy. Int J Radiat Oncol Biol Phys. 64:38–46. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Sadri N and Zhang PJ: Hypoxia-inducible factors: Mediators of cancer progression; prognostic and therapeutic targets in soft tissue sarcomas. Cancers (Basel). 5:320–333. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Martinive P, Defresne F, Bouzin C, Saliez J, Lair F, Grégoire V, Michiels C, Dessy C and Feron O: Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: Implications for anticancer therapies. Cancer Res. 66:11736–11744. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Dewhirst MW, Cao Y and Moeller B: Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 8:425–437. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Zhang C, Yang X, Zhang Q, Yang B, Xu L, Qin Q, Zhu H, Liu J, Cai J, Tao G, et al: Berberine radiosensitizes human nasopharyngeal carcinoma by suppressing hypoxia-inducible factor-1alpha expression. Acta Otolaryngol. 134:185–192. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Meijer TW, Kaanders JH, Span PN and Bussink J: Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res. 18:5585–5594. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Schmitt JM, Sommers SR, Fisher W, Ansari R, Robin E, Koneru K, McClean J, Liu Z, Tong Y and Hanna N: Sunitinib plus paclitaxel in patients with advanced esophageal cancer: A phase II study from the Hoosier Oncology Group. J Thorac Oncol. 7:760–763. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Chen FH, Chiang CS, Wang CC, Fu SY, Tsai CS, Jung SM, Wen CJ, Lee CC and Hong JH: Vasculatures in tumors growing from preirradiated tissues: Formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Int J Radiat Oncol Biol Phys. 80:1512–1521. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Gaustad JV, Pozdniakova V, Hompland T, Simonsen TG and Rofstad EK: Magnetic resonance imaging identifies early effects of sunitinib treatment in human melanoma xenografts. J Exp Clin Cancer Res. 32:932013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ding YQ, Qin Q, Yang Y, Sun XC, Yang X, Zhu HC, Chen XC, Zhang H, Yang YH, Gao L, Gao L, et al: Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment. Oncol Lett 12: 4671-4676, 2016.
APA
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H. ... Zhou, X. (2016). Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment. Oncology Letters, 12, 4671-4676. https://doi.org/10.3892/ol.2016.5247
MLA
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H., Chen, X., Zhang, H., Yang, Y., Gao, L., Luo, J., Zhou, X."Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment". Oncology Letters 12.6 (2016): 4671-4676.
Chicago
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H., Chen, X., Zhang, H., Yang, Y., Gao, L., Luo, J., Zhou, X."Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment". Oncology Letters 12, no. 6 (2016): 4671-4676. https://doi.org/10.3892/ol.2016.5247
Copy and paste a formatted citation
x
Spandidos Publications style
Ding YQ, Qin Q, Yang Y, Sun XC, Yang X, Zhu HC, Chen XC, Zhang H, Yang YH, Gao L, Gao L, et al: Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment. Oncol Lett 12: 4671-4676, 2016.
APA
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H. ... Zhou, X. (2016). Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment. Oncology Letters, 12, 4671-4676. https://doi.org/10.3892/ol.2016.5247
MLA
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H., Chen, X., Zhang, H., Yang, Y., Gao, L., Luo, J., Zhou, X."Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment". Oncology Letters 12.6 (2016): 4671-4676.
Chicago
Ding, Y., Qin, Q., Yang, Y., Sun, X., Yang, X., Zhu, H., Chen, X., Zhang, H., Yang, Y., Gao, L., Luo, J., Zhou, X."Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment". Oncology Letters 12, no. 6 (2016): 4671-4676. https://doi.org/10.3892/ol.2016.5247
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