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
July-2017 Volume 14 Issue 1

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
July-2017 Volume 14 Issue 1

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 Open Access

Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer

  • Authors:
    • Fajiu Li
    • Jie Huang
    • Dongyuan Ji
    • Qinghua Meng
    • Chuanhai Wang
    • Shi Chen
    • Xiaojiang Wang
    • Zhiyang Zhu
    • Cheng Jiang
    • Yi Shi
    • Shuang Liu
    • Chenghong Li
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Wuhan No. 6 Hospital, Affiliated Hospital to Jianghan University, Wuhan, Hubei 430072, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 89-96
    |
    Published online on: April 28, 2017
       https://doi.org/10.3892/ol.2017.6103
  • 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

Tumor angiogenesis is essential during lung cancer development and targeting angiogenesis may possess a potential therapeutic value. The present study demonstrates that azithromycin, a Food and Drug Administration‑approved antibiotic drug, is a novel tumor angiogenesis inhibitor. Azithromycin inhibits capillary network formation of human lung tumor associated‑endothelial cells (HLT‑ECs) in vitro and in vivo. It significantly inhibits HLT‑EC adhesion and vascular endothelial growth factor (VEGF)‑induced proliferation of HLT‑ECs in a dose‑dependent manner without affecting migration. In addition, azithromycin induces apoptosis of HLT‑ECs even in the presence of VEGF. Notably, azithromycin inhibits proliferation and induces apoptosis in multiple lung cancer cell lines to a significantly reduced extent compared with in HLT‑ECs, suggesting that HLT‑ECs are more susceptible to azithromycin treatment. In a lung tumor xenograft model, azithromycin significantly inhibits tumor growth and its anti‑tumor activities are achieved by suppressing angiogenesis. Notably, the inhibitory effects of azithromycin on angiogenesis are associated with its ability to suppress VEGF‑induced activation of VEGF receptor 2 (VEGFR2), phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt), focal adhesion kinase, and disruption of focal adhesion assembly and actin stress fiber formation in HLT‑ECs. The present study identifies that azithromycin targets VEGFR2‑mediated focal adhesion and PI3K/Akt signaling pathways in HLT‑ECs, leading to the suppression of angiogenesis and lung tumor growth.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Dancey J and Le Chevalier T: Non-small cell lung cancer: An overview of current management. Eur J Cancer. 33 Suppl 1:S2–S7. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Blumenschein GR Jr, Reckamp K, Stephenson GJ, O'Rourke T, Gladish G, McGreivy J, Sun YN, Ye Y, Parson M and Sandler A: Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer. Clin Cancer Res. 16:279–290. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Lind JS and Smit EF: Angiogenesis inhibitors in the treatment of non-small cell lung cancer. Ther Adv Med Oncol. 1:95–107. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Folkman J: Tumor angiogenesis: Therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI

6 

Ferrara N: The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat. 36:127–137. 1995. View Article : Google Scholar : PubMed/NCBI

7 

Han H, Silverman JF, Santucci TS, Macherey RS, d'Amato TA, Tung MY, Weyant RJ and Landreneau RJ: Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol. 8:72–79. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Fontanini G, Bigini D, Vignati S, Basolo F, Mussi A, Lucchi M, Chine S, Angeletti CA, Harris AL and Bevilacqua G: Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol. 177:57–63. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Horn L and Sandler AB: Angiogenesis in the treatment of non-small cell lung cancer. Proc Am Thorac Soc. 6:pp. 206–217. 2009; View Article : Google Scholar : PubMed/NCBI

10 

Zhao L, Li W, Zhang H, Hou N, Guo L and Gao Q: Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: A pooled analysis of randomized controlled trials. Onco Targets Ther. 8:2775–2781. 2015.PubMed/NCBI

11 

Zhang TT, Wang RM, Yang Z and Chen GB: Dual inhibiting EGFR and VEGF pathways versus EGFR-TKIs alone in the treatment of advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials. Clin Transl Oncol. 18:576–581. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Zhang J, Liu J, Chen H, Wu W, Li X, Wu Y, Zhang K and Gu L: The impact of histological types on the efficacy of angiogenesis inhibitors in the treatment of advanced NSCLC: A meta-analysis of randomized controlled trials. Onco Targets Ther. 8:2375–2382. 2015.PubMed/NCBI

13 

Esposito S, Bosis S, Faelli N, Begliatti E, Droghetti R, Tremolati E, Porta A, Blasi F and Principi N: Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections. Pediatr Infect Dis J. 24:438–444. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Champney WS and Burdine R: Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus. Antimicrob Agents Chemother. 39:2141–2144. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Kitsiouli E, Antoniou G, Gotzou H, Karagiannopoulos M, Basagiannis D, Christoforidis S, Nakos G and Lekka ME: Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells. Biochim Biophys Acta. 1852:1288–1297. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F and Lisanti MP: Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease. Oncotarget. 6:4569–4584. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Zhou X, Zhang Y, Li Y, Hao X, Liu X and Wang Y: Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells. Cancers (Basel). 4:1318–1332. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Chu DJ, Yao DE, Zhuang YF, Hong Y, Zhu XC, Fang ZR, Yu J and Yu ZY: Azithromycin enhances the favorable results of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. Genet Mol Res. 13:2796–2805. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Guedez L, Rivera AM, Salloum R, Miller ML, Diegmueller JJ, Bungay PM and Stetler-Stevenson WG: Quantitative assessment of angiogenic responses by the directed in vivo angiogenesis assay. Am J Pathol. 162:1431–1439. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Madri JA and Pratt BM: Endothelial cell-matrix interactions: In vitro models of angiogenesis. J Histochem Cytochem. 34:85–91. 1986. View Article : Google Scholar : PubMed/NCBI

21 

Davis GE and Senger DR: Endothelial extracellular matrix: Biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res. 97:1093–1107. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Ferrara N: The role of VEGF in the regulation of physiological and pathological angiogenesis. EXS. 209–231. 2005.PubMed/NCBI

23 

Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW and Martin GR: Basement membrane complexes with biological activity. Biochemistry. 25:312–318. 1986. View Article : Google Scholar : PubMed/NCBI

24 

Shibuya M: Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep. 41:278–286. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Lechertier T and Hodivala-Dilke K: Focal adhesion kinase and tumour angiogenesis. J Pathol. 226:404–412. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Parums DV, Cordell JL, Micklem K, Heryet AR, Gatter KC and Mason DY: JC70: A new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. J Clin Pathol. 43:752–757. 1990. View Article : Google Scholar : PubMed/NCBI

27 

Karar J and Maity A: PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci. 4:512011. View Article : Google Scholar : PubMed/NCBI

28 

Kim GD, Oh J, Park HJ, Bae K and Lee SK: Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Int J Oncol. 43:600–610. 2013.PubMed/NCBI

29 

He L, Wu Y, Lin L, Wang J, Wu Y, Chen Y, Yi Z, Liu M and Pang X: Hispidulin, a small flavonoid molecule, suppresses the angiogenesis and growth of human pancreatic cancer by targeting vascular endothelial growth factor receptor 2-mediatedPI3K/Akt/mTOR signaling pathway. Cancer Sci. 102:219–225. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li F, Huang J, Ji D, Meng Q, Wang C, Chen S, Wang X, Zhu Z, Jiang C, Shi Y, Shi Y, et al: Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer. Oncol Lett 14: 89-96, 2017.
APA
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S. ... Li, C. (2017). Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer. Oncology Letters, 14, 89-96. https://doi.org/10.3892/ol.2017.6103
MLA
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S., Wang, X., Zhu, Z., Jiang, C., Shi, Y., Liu, S., Li, C."Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer". Oncology Letters 14.1 (2017): 89-96.
Chicago
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S., Wang, X., Zhu, Z., Jiang, C., Shi, Y., Liu, S., Li, C."Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer". Oncology Letters 14, no. 1 (2017): 89-96. https://doi.org/10.3892/ol.2017.6103
Copy and paste a formatted citation
x
Spandidos Publications style
Li F, Huang J, Ji D, Meng Q, Wang C, Chen S, Wang X, Zhu Z, Jiang C, Shi Y, Shi Y, et al: Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer. Oncol Lett 14: 89-96, 2017.
APA
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S. ... Li, C. (2017). Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer. Oncology Letters, 14, 89-96. https://doi.org/10.3892/ol.2017.6103
MLA
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S., Wang, X., Zhu, Z., Jiang, C., Shi, Y., Liu, S., Li, C."Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer". Oncology Letters 14.1 (2017): 89-96.
Chicago
Li, F., Huang, J., Ji, D., Meng, Q., Wang, C., Chen, S., Wang, X., Zhu, Z., Jiang, C., Shi, Y., Liu, S., Li, C."Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2‑mediated signaling pathways in lung cancer". Oncology Letters 14, no. 1 (2017): 89-96. https://doi.org/10.3892/ol.2017.6103
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