Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

This article was retracted on 17 April 2017

Abstract

Vascular endothelial growth factor (VEGF) is one of the most effective angiogenic factors that promote generation of tumor vasculature. VEGF is usually up-regulated in multiple cancers including osteosarcoma and glioma. To further explore the potential molecular mechanism that inhibits tumor growth induced by interference of VEGF expression, we constructed a Lv-shVEGF vector and assessed the efficiency of VEGF silencing and its influence in U2OS cells. The data demonstrate that Lv-shVEGF has high inhibition efficiency on VEGF expression, which inhibits proliferation and promotes apoptosis of U2OS cells in vitro. Our results also indicate that inhibition of VEGF expression suppresses osteosarcoma tumor growth in vivo and reduces osteosarcoma angiogenesis. We also found that the activations of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were considerably reduced after osteosarcoma cells were treated with Lv-shVEGF. Taken together, our data demonstrate that VEGF silencing suppresses cell proliferation, promotes cell apoptosis, and reduces osteosarcoma angiogenesis through inactivation of PI3K/AKT signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Wang, S. W., et al. (2014). CCL5/CCR5 axis induces vascular endothelial growth factor-mediated tumor angiogenesis in human osteosarcoma microenvironment. Carcinogenesis, 35(12), 2633–2642.

    Article  CAS  Google Scholar 

  2. Xu, M., et al. (2014). Adenovirus-mediated ING4 gene transfer in osteosarcoma suppresses tumor growth via induction of apoptosis and inhibition of tumor angiogenesis. Technology Cancer Research and Treatment. doi:10.7785/tcrt.2012.500424.

    Google Scholar 

  3. DuBois, S., & Demetri, G. (2007). Markers of angiogenesis and clinical features in patients with sarcoma. Cancer, 109(5), 813–819.

    Article  CAS  PubMed  Google Scholar 

  4. Mikulic, D., et al. (2004). Tumor angiogenesis and outcome in osteosarcoma. Journal of Pediatric Hematology Oncology, 21(7), 611–619.

    Article  PubMed  Google Scholar 

  5. Jendreyko, N., et al. (2005). Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo. Proceedings of the National Academy of Sciences of the United States of America, 102(23), 8293–8298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mosch, B., et al. (2010). Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis. Jounal of Oncology, 2010, 135285.

    Google Scholar 

  7. Jin, X., et al. (2011). EGFR-AKT-Smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction. Cancer Research, 71(22), 7125–7134.

    Article  CAS  PubMed  Google Scholar 

  8. Weiss, K. R., et al. (2006). VEGF and BMP expression in mouse osteosarcoma cells. Clinical Orthopaedics and Related Research, 450, 111–117.

    Article  PubMed  Google Scholar 

  9. Won, Y. W., et al. (2012). Post-translational regulated and hypoxia-responsible VEGF plasmid for efficient secretion. Journal of Controlled Release, 160(3), 525–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wei, M. H., et al. (1996). Localization of the human vascular endothelial growth factor gene, VEGF, at chromosome 6p12. Human Genetics, 97(6), 794–797.

    Article  CAS  PubMed  Google Scholar 

  11. Leidi, M., Mariotti, M., & Maier, J. A. (2010). EDF-1 contributes to the regulation of nitric oxide release in VEGF-treated human endothelial cells. European Journal of Cell Biology, 89(9), 654–660.

    Article  CAS  PubMed  Google Scholar 

  12. Zhu, K. Q., et al. (2005). Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar. Burns, 31(1), 5–10.

    Article  PubMed  Google Scholar 

  13. Baker, G. J., et al. (2014). Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy. Neoplasia, 16(7), 543–561.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lee, L., et al. (2006). Biomarkers for assessment of pharmacologic activity for a vascular endothelial growth factor (VEGF) receptor inhibitor, PTK787/ZK 222584 (PTK/ZK): translation of biological activity in a mouse melanoma metastasis model to phase I studies in patients with advanced colorectal cancer with liver metastases. Cancer Chemotherapy and Pharmacology, 57(6), 761–771.

    Article  CAS  PubMed  Google Scholar 

  15. Fukuhara, M., et al. (2005). Re-expression of reduced VEGF activity in liver metastases of experimental pancreatic cancer. Journal of Nippon Medical School, 72(3), 155–164.

    Article  CAS  PubMed  Google Scholar 

  16. Ohba, T., et al. (2014). Autocrine VEGF/VEGFR1 signaling in a subpopulation of cells associates with aggressive osteosarcoma. Molecular Cancer Research, 12(8), 1100–1111.

    Article  CAS  PubMed  Google Scholar 

  17. Roorda, B. D., et al. (2010). VEGF-A promotes lymphoma tumour growth by activation of STAT proteins and inhibition of p27(KIP1) via paracrine mechanisms. European Journal of Cancer, 46(5), 974–982.

    Article  CAS  PubMed  Google Scholar 

  18. Kawashima, H., et al. (2003). Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: efficacy of adenoviral gene therapy for osteosarcoma. Cancer Science, 94(1), 70–75.

    Article  CAS  PubMed  Google Scholar 

  19. Yamaguchi, H., et al. (1988). The alteration in the pattern of pulmonary metastasis with adjuvant chemotherapy in osteosarcoma. International Orthopaedics, 12(4), 305–308.

    Article  CAS  PubMed  Google Scholar 

  20. Bielack, S., Carrle, D., & Jost, L. (2008). Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. The Annals of Oncology, 19(Suppl 2), ii94–ii96.

    PubMed  Google Scholar 

  21. Courties, G., et al. (2009). RNA interference-based gene therapy for successful treatment of rheumatoid arthritis. Expert Opinion on Biological Therapy, 9(5), 535–538.

    Article  CAS  PubMed  Google Scholar 

  22. Valdehita, A., et al. (2012). RNA interference-directed silencing of VPAC1 receptor inhibits VIP effects on both EGFR and HER2 transactivation and VEGF secretion in human breast cancer cells. Molecular and Cellular Endocrinology, 348(1), 241–246.

    Article  PubMed  Google Scholar 

  23. Qi, L., et al. (2014). Effects of VEGF suppression by small hairpin RNA interference combined with radiotherapy on the growth of cervical cancer. Genetics and Molecular Research, 13(3), 5094–5106.

    Article  CAS  PubMed  Google Scholar 

  24. Majeti, B. K., et al. (2013). VEGF is an important mediator of tumor angiogenesis in malignant lesions in a genetically engineered mouse model of lung adenocarcinoma. BMC Cancer, 13, 213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wu, J., et al. (2012). Short Hairpin RNA (shRNA) Ether a go–go 1 (Eag1) inhibition of human osteosarcoma angiogenesis via VEGF/PI3 K/AKT signaling. International Journal of Molecular Sciences, 13(10), 12573–12583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kitamura, T., et al. (2008). Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nature Cell Biology, 10(3), 329–337.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Tangdu Hospital, Orthopedics Oncology Institute of Chinese PLA, Fourth Military Medical University, NO 569 XinSi Road, Xi’an, 710038, Shanxi Province, China

    Jian Zhao, Zi-Ru Zhang, Bao-An Ma & Qing-Yu Fan

  2. Outpatient Department, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, Shanxi Province, China

    Na Zhao

Authors
  1. Jian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zi-Ru Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Na Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bao-An Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing-Yu Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-Yu Fan.

Additional information

Due to dual submission, the Editor in Chief of CBBI wishes to retract this article. Zhao J, Zhang ZR, Zhao N, Ma BA, Fan QY. VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway. Cell Biochem Biophys. 2015 Nov;73(2):519-25. DOI: 10.1007/s12013-015-0692-7

Zhao J, Zhang ZR, Zhao N, Ma BA, Fan QY. VEGF silencing inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via PI3K/AKT signaling pathway. Int J Clin Exp Med. 2015 Aug 15;8(8):12411-7

An erratum to this article is available at http://dx.doi.org/10.1007/s12013-017-0794-5.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, J., Zhang, ZR., Zhao, N. et al. RETRACTED ARTICLE: VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway. Cell Biochem Biophys 73, 519–525 (2015). https://doi.org/10.1007/s12013-015-0692-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-015-0692-7

Keywords

Search

Navigation