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
January-2016 Volume 11 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
January-2016 Volume 11 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

Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo

  • Authors:
    • Wen-Hui Ma
    • Yong-Chao Liu
    • Mei-Lan Xue
    • Zheng Zheng
    • Yin-Lin Ge
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 159-167
    |
    Published online on: November 5, 2015
       https://doi.org/10.3892/ol.2015.3870
  • 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

Metastasis constantly occurs in the majority of cases of primary breast cancer at late stage or following surgical treatment. Survivin, a member of the inhibitor of apoptosis protein family, has long been recognized as a promising anticancer target, but its antitumor effects remain largely unexplored. In order to elucidate the role of survivin in breast cancer metastasis, short interfering RNA (siRNA) was used in the present study to specifically downregulate survivin expression in the murine breast cancer cell line 4T1. The results demonstrated that blocking the expression of survivin by siRNA inhibited the proliferation, migration and invasion abilities of murine breast cancer cells in vitro. Vascular endothelial growth factor (VEGF)‑C is a lymphatic endothelial cell‑stimulating factor that may lead to the formation of lymphatic vessels in lymph nodes. In the present study, the inhibition of survivin by siRNA was able to reduce the overexpression of VEGF‑C in 4T1 cells. Furthermore, intratumoral injections of the survivin‑siRNA significantly inhibited the growth of orthotopically transplanted 4T1 tumors in vivo. In addition, the number of pulmonary metastases and the microlymphatic vessel density were significantly reduced in vivo, following transfection with survivin‑siRNA. The results of the present study suggested that the Akt/hypoxia‑inducible factor‑1α signaling pathway participates in the survivin‑mediated downregulation of VEGF‑C expression observed in breast cancer cells treated with survivin‑siRNA. Therefore, the use of siRNA specifically targeting survivin may be a potential anticancer method in the future.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011.(Erratum in CA Cancer J Clin 61: 134, 2011). View Article : Google Scholar : PubMed/NCBI

2 

Ali SM, Harvey HA and Lipton A: Metastatic breast cancer: Overview of treatment. Clin Orthop Relat Res. 415(Suppl): S132–S137. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Bidard FC, Fehm T, Ignatiadis M, Smerage JB, Alix-Panabières C, Janni W, Messina C, Paoletti C, Müller V, Hayes DF, et al: Clinical application of circulating tumor cells in breast cancer: Overview of the current interventional trials. Cancer Metastasis Rev. 32:179–188. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Mackey JR, Kerbel RS, Gelmon KA, et al: Controlling angiogenesis in breast cancer: A systematic review of anti-angiogenic trials. Cancer Treat Rev. 38:673–688. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Ran S, Volk L, Hall K and Flister MJ: Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology. 17:229–251. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Carter CL, Allen C and Henson DE: Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 63:181–187. 1989. View Article : Google Scholar : PubMed/NCBI

7 

Timoshenko AV, Rastogi S and Lala PK: Migration-promoting role of VEGF-C and VEGF-C binding receptors in human breast cancer cells. Br J Cancer. 97:1090–1098. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Sun P, Gao J, Liu YL, Wei LW, Wu LP and Liu ZY: RNA interference (RNAi)-mediated vascular endothelial growth factor-C (VEGF-C) reduction interferes with lymphangiogenesis and enhances epirubicin sensitivity of breast cancer cells. Mol Cell Biochem. 308:161–168. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N and Alitalo K: A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO. 15:290–298. 1996.

10 

Valtola R, Salven P, Heikkilä P, Taipale J, Joensuu H, Rehn M, Pihlajaniemi T, Weich H, de Waal R and Alitalo K: VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol. 154:1381–1390. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S and Sugimachi K: Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer. Breast Cancer Res Treat. 66:159–164. 2011. View Article : Google Scholar

12 

Chen Z, Varney ML, Backora MW, Cowan K, Solheim JC, Talmadge JE and Singh RK: Down-regulation of vascular endothelial cell growth factor-C expression using small interfering RNA vectors in mammary tumors inhibits tumor lymphangiogenesis and spontaneous metastasis and enhances survival. Cancer Res. 65:9004–9011. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Cai X, Ma S, Gu M, Zu C, Qu W and Zheng X: Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast cancer. Diagn Pathol. 7:522012. View Article : Google Scholar : PubMed/NCBI

14 

Ambrosini G, Adida C and Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 3:917–921. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Suzuki A, Ito T, Kawano H, Hayashida M, Hayasaki Y, Tsutomi Y, Akahane K, Nakano T, Miura M and Shiraki K: Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene. 19:1346–1353. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Altieri DC: Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 3:46–54. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Altieri DC: Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene. 22:8581–8589. 2003. View Article : Google Scholar : PubMed/NCBI

18 

McKenzie JA, Liu T, Goodson AG and Grossman D: Survivin enhances motility of melanoma cells by supporting Akt activation and {α}5 integrin upregulation. Cancer Res. 70:7927–7937. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T and Altieri DC: IAP regulation of metastasis. Cancer Cell. 17:53–64. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Marioni G, Bertolin A, Giacomelli L, Marchese-Ragona R, Savastano M, Calgaro N, Marino F, De Filippis C and Staffieri A: Expression of the apoptosis inhibitor protein Survivin in primary laryngeal carcinoma and cervical lymph node metastasis. Anticancer Res. 26:3813–3817. 2006.PubMed/NCBI

21 

Kedinger V, Meulle A, Zounib O, et al: Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases. BMC Cancer. 13:3382013. View Article : Google Scholar : PubMed/NCBI

22 

Ikehara M, Oshita F, Kameda Y, Ito H, Ohgane N, Suzuki R, Saito H, Yamada K, Noda K and Mitsuda A: Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung. Oncol Rep. 9:835–838. 2002.PubMed/NCBI

23 

Li X, Dang X and Sun X: Expression of survivin and VEGF-C in breast cancer tissue and its relation to lymphatic metastasis. Eur J Gynaecol Oncol. 33:178–182. 2012.PubMed/NCBI

24 

Xue M, Ge Y, Zhang J, Liu Y, Wang Q, Hou L and Zheng Z: Fucoidan inhibited 4T1 mouse breast cancer cell growth in vivo and in vitro via downregulation of Wnt/β-catenin signaling. Nutr Cancer. 65:460–468. 2013. View Article : Google Scholar : PubMed/NCBI

25 

National Institutes of Health, Department of Health and Human Services. Guide for the Care and Use of Laboratory Animals (Guide) (revised 1985). NIH Publication No. 85–23. (Bethesda). National Institutes of Health. 1989.

26 

Xue M, Ge Y, Zhang J, Wang Q, Hou L, Liu Y, Sun L and Li Q: Anticancer properties and mechanisms of fucoidan on mouse breast cancer in vitro and in vivo. PloS One. 7:e434832012. View Article : Google Scholar : PubMed/NCBI

27 

Dong XP, Xiao TH, Dong H, Jiang N and Zhao XG: Endostar combined with cisplatin inhibits tumor growth and lymphatic metastasis of lewis lung carcinoma xenografts in mice. Asian Pac J Cancer Prev. 14:3079–3083. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 396:580–584. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Hirakawa S, Brown LF, Kodama S, Paavonen K, Alitalo K and Detmar M: VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood. 109:1010–1017. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K and Detmar M: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 7:192–198. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Xia H, Mao Q, Paulson HL and Davidson BL: siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol. 20:1006–1010. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Shim MS and Kwon YJ: Efficient and targeted delivery of siRNA in vivo. FEBS J. 23:4814–4827. 2010. View Article : Google Scholar

33 

Brito LGO, Schiavon VF, Andrade JM, Tiezzi DG, Peria FM and Marana HR: Expression of Hypoxia-inducible factor 1-α and vascular endothelial growth factor-C in locally advanced breast cancer patients. Clinics. 66:1313–1320. 2011.PubMed/NCBI

34 

Song G, Ouyang G and Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9:59–71. 2005. View Article : Google Scholar : PubMed/NCBI

35 

West KA, Castillo SS and Dennis PA: Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat. 5:234–248. 2002. View Article : Google Scholar : PubMed/NCBI

36 

Goc A, Al-Husein B, Kochuparambil ST, Liu J, Heston WW and Somanath PR: PI3 kinase integrates Akt and MAP kinase signaling pathways in the regulation of prostate cancer. Int J Oncol. 38:267–277. 2011.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma W, Liu Y, Xue M, Zheng Z and Ge Y: Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo. Oncol Lett 11: 159-167, 2016.
APA
Ma, W., Liu, Y., Xue, M., Zheng, Z., & Ge, Y. (2016). Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo. Oncology Letters, 11, 159-167. https://doi.org/10.3892/ol.2015.3870
MLA
Ma, W., Liu, Y., Xue, M., Zheng, Z., Ge, Y."Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo". Oncology Letters 11.1 (2016): 159-167.
Chicago
Ma, W., Liu, Y., Xue, M., Zheng, Z., Ge, Y."Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo". Oncology Letters 11, no. 1 (2016): 159-167. https://doi.org/10.3892/ol.2015.3870
Copy and paste a formatted citation
x
Spandidos Publications style
Ma W, Liu Y, Xue M, Zheng Z and Ge Y: Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo. Oncol Lett 11: 159-167, 2016.
APA
Ma, W., Liu, Y., Xue, M., Zheng, Z., & Ge, Y. (2016). Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo. Oncology Letters, 11, 159-167. https://doi.org/10.3892/ol.2015.3870
MLA
Ma, W., Liu, Y., Xue, M., Zheng, Z., Ge, Y."Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo". Oncology Letters 11.1 (2016): 159-167.
Chicago
Ma, W., Liu, Y., Xue, M., Zheng, Z., Ge, Y."Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo". Oncology Letters 11, no. 1 (2016): 159-167. https://doi.org/10.3892/ol.2015.3870
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