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
July-2017 Volume 38 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 38 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

Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth

  • Authors:
    • Eryun Zhang
    • Hailian Shi
    • Li Yang
    • Xiaojun Wu
    • Zhengtao Wang
  • View Affiliations / Copyright

    Affiliations: Shanghai Key Laboratory of Complex Prescriptions, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
  • Pages: 359-367
    |
    Published online on: May 19, 2017
       https://doi.org/10.3892/or.2017.5652
  • 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

Blockade of angiogenesis is an important approach for cancer treatment and prevention. In the present study, we investigated the effect of ginsenoside Rd (Rd) on angiogenesis in vitro and in vivo. Our results demonstrated that Rd inhibited vascular endothelial growth factor (VEGF)-induced migration, tube formation and proliferation of primary cultured human umbilical vascular endothelial cells (HUVECs) dose‑dependently. Furthermore, Rd abrogated VEGF-induced sprouting of the vessels from aortic rings, and inhibited vascular formation in the Matrigel plug assay in vivo. Under normoxic or hypoxic conditions, Rd suppressed VEGF‑induced activation of Akt/mammalian target of rapamycin (mTOR) signaling transduction cascades in HUVECs. When intraperitoneally administered to mice bearing human breast cancer (MDA‑MB-231) cell xenografts, Rd significantly decreased the volume and the weight of solid tumors in a dose-dependent manner, and decreased tumor angiogenesis as less Ki67- and CD31-positive cells were found. Additionally, we found that Rd inhibited proliferation and induced apoptosis as well as the inhibition of Akt/mTOR/P70S6 kinase signaling in breast cancer cells. Collectively, our findings revealed that Rd may be a promising anti-angiogenic drug with significant antitumor activity in human breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1:27–31. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Potente M, Gerhardt H and Carmeliet P: Basic and therapeutic aspects of angiogenesis. Cell. 146:873–887. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Gao W, Chang G, Wang J, Jin W, Wang L, Lin Y, Li H, Ma L, Li Q and Pang T: Inhibition of K562 leukemia angiogenesis and growth by selective Na+/H+ exchanger inhibitor cariporide through down-regulation of pro-angiogenesis factor VEGF. Leuk Res. 35:1506–1511. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Otrock ZK, Mahfouz RA, Makarem JA and Shamseddine AI: Understanding the biology of angiogenesis: Review of the most important molecular mechanisms. Blood Cells Mol Dis. 39:212–220. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Thairu N, Kiriakidis S, Dawson P and Paleolog E: Angiogenesis as a therapeutic target in arthritis in 2011: Learning the lessons of the colorectal cancer experience. Angiogenesis. 14:223–234. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Weis SM and Cheresh DA: Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat Med. 17:1359–1370. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Folkman J: Angiogenesis: An organizing principle for drug discovery? Nat Rev Drug Discov. 6:273–286. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Adams RH and Alitalo K: Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 8:464–478. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ and Holash J: Vascular-specific growth factors and blood vessel formation. Nature. 407:242–248. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Jiang BH: PI3K/AKT and mTOR/p70S6K1 signaling pathways in human cancer. Curr Cancer Drug Targets. 13:2332013. View Article : Google Scholar : PubMed/NCBI

11 

Jiang BH and Liu LZ: AKT signaling in regulating angiogenesis. Curr Cancer Drug Targets. 8:19–26. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT and De Bruijn EA: Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 56:549–580. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Chen CF, Chiou WF and Zhang JT: Comparison of the pharmacological effects of Panax ginsengPanax quinquefolium. Acta Pharmacol Sin. 29:1103–1108. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Ng TB: Pharmacological activity of sanchi ginseng (Panax notoginseng). J Pharm Pharmacol. 58:1007–1019. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Christensen LP: Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 55:1–99. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Xie Z, Shi M, Zhang C, Zhao H, Hui H and Zhao G: Ginsenoside Rd protects against cerebral ischemia-reperfusion injury via decreasing the expression of the NMDA receptor 2B subunit and its phosphorylated product. Neurochem Res. 41:2149–2159. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Zeng X, Li J and Li Z: Ginsenoside Rd mitigates myocardial ischemia-reperfusion injury via Nrf2/HO-1 signaling pathway. Int J Clin Exp Med. 8:14497–14504. 2015.PubMed/NCBI

18 

Kim BJ: Involvement of melastatin type transient receptor potential 7 channels in ginsenoside Rd-induced apoptosis in gastric and breast cancer cells. J Ginseng Res. 37:201–209. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Lee SY, Kim GT, Roh SH, Song JS, Kim HJ, Hong SS, Kwon SW and Park JH: Proteome changes related to the anti-cancer activity of HT29 cells by the treatment of ginsenoside Rd. Pharmazie. 64:242–247. 2009.PubMed/NCBI

20 

Yang ZG, Sun HX and Ye YP: Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis. Chem Biodivers. 3:187–197. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Park HJ, Zhang Y, Georgescu SP, Johnson KL, Kong D and Galper JB: Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Rev. 2:93–102. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Yi T, Yi Z, Cho SG, Luo J, Pandey MK, Aggarwal BB and Liu M: Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling. Cancer Res. 68:1843–1850. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Nicosia RF and Ottinetti A: Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: A comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell Dev Biol. 26:119–128. 1990. View Article : Google Scholar : PubMed/NCBI

24 

Malinda KM: In vivo Matrigel migration and angiogenesis assay. Methods Mol Biol. 467:287–294. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Gasparini G, Longo R, Toi M and Ferrara N: Angiogenic inhibitors: A new therapeutic strategy in oncology. Nat Clin Pract Oncol. 2:562–577. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Fujii T, Yonemitsu Y, Onimaru M, Inoue M, Hasegawa M, Kuwano H and Sueishi K: VEGF function for upregulation of endogenous PlGF expression during FGF-2-mediated therapeutic angiogenesis. Atherosclerosis. 200:51–57. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev. 18:1926–1945. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Liu S, Wu P, Ye D, Huang Y, Zhou X, Li Y and Cai L: Effects of lipoxin A4 on CoCl2-induced angiogenesis and its possible mechanisms in human umbilical vein endothelial cells. Pharmacology. 84:17–23. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Loboda A, Jazwa A, Wegiel B, Jozkowicz A and Dulak J: Heme oxygenase-1-dependent and -independent regulation of angiogenic genes expression: Effect of cobalt protoporphyrin and cobalt chloride on VEGF and IL-8 synthesis in human microvascular endothelial cells. Cell Mol Biol. 51:347–355. 2005.PubMed/NCBI

31 

Ferrara N and Kerbel RS: Angiogenesis as a therapeutic target. Nature. 438:967–974. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Reuben SC, Gopalan A, Petit DM and Bishayee A: Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer. Mol Nutr Food Res. 56:14–29. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Holash J, Wiegand SJ and Yancopoulos GD: New model of tumor angiogenesis: Dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene. 18:5356–5362. 1999. View Article : Google Scholar : PubMed/NCBI

34 

Lamalice L, Le Boeuf F and Huot J: Endothelial cell migration during angiogenesis. Circ Res. 100:782–794. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Stotz M, Gerger A, Haybaeck J, Kiesslich T, Bullock MD and Pichler M: Molecular targeted therapies in hepatocellular carcinoma: Past, present and future. Anticancer Res. 35:5737–5744. 2015.PubMed/NCBI

36 

Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, et al: VEGF-Trap: A VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 99:11393–11398. 2002. View Article : Google Scholar : PubMed/NCBI

37 

Ferrara N: Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 9 Suppl 1:S2–S10. 2004. View Article : Google Scholar

38 

Noble ME, Endicott JA and Johnson LN: Protein kinase inhibitors: Insights into drug design from structure. Science. 303:1800–1805. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Radisavljevic Z: AKT as locus of cancer angiogenic robustness and fragility. J Cell Physiol. 228:21–24. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Ciuffreda L, Di Sanza C, Incani UC and Milella M: The mTOR pathway: A new target in cancer therapy. Curr Cancer Drug Targets. 10:484–495. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Liu LZ, Zheng JZ, Wang XR and Jiang BH: Endothelial p70 S6 kinase 1 in regulating tumor angiogenesis. Cancer Res. 68:8183–8188. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Bhushan S, Kumar A, Malik F, Andotra SS, Sethi VK, Kaur IP, Taneja SC, Qazi GN and Singh J: A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells. Apoptosis. 12:1911–1926. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang E, Shi H, Yang L, Wu X and Wang Z: Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncol Rep 38: 359-367, 2017.
APA
Zhang, E., Shi, H., Yang, L., Wu, X., & Wang, Z. (2017). Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncology Reports, 38, 359-367. https://doi.org/10.3892/or.2017.5652
MLA
Zhang, E., Shi, H., Yang, L., Wu, X., Wang, Z."Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth". Oncology Reports 38.1 (2017): 359-367.
Chicago
Zhang, E., Shi, H., Yang, L., Wu, X., Wang, Z."Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth". Oncology Reports 38, no. 1 (2017): 359-367. https://doi.org/10.3892/or.2017.5652
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang E, Shi H, Yang L, Wu X and Wang Z: Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncol Rep 38: 359-367, 2017.
APA
Zhang, E., Shi, H., Yang, L., Wu, X., & Wang, Z. (2017). Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncology Reports, 38, 359-367. https://doi.org/10.3892/or.2017.5652
MLA
Zhang, E., Shi, H., Yang, L., Wu, X., Wang, Z."Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth". Oncology Reports 38.1 (2017): 359-367.
Chicago
Zhang, E., Shi, H., Yang, L., Wu, X., Wang, Z."Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth". Oncology Reports 38, no. 1 (2017): 359-367. https://doi.org/10.3892/or.2017.5652
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