Cell Biochemistry and Biophysics

, Volume 72, Issue 1, pp 251–257 | Cite as

Downregulation of Survivin by shRNA Inhibits Invasion and Enhances the Radiosensitivity of Laryngeal Squamous Cell Carcinoma

Original Paper

Abstract

Radiotherapy is an important treatment modality for laryngeal carcinoma, however, some patients with early stage laryngeal carcinomas showed resistance to radiotherapy. Survivin overexpression is associated with radioresistance of laryngeal squamous cell carcinoma. We speculated that the inhibition of survivin expression might improve the radiosensitivity of laryngeal carcinoma. We assessed the effect of survivin expressions by shRNA on the radiosensitivity of laryngeal squamous cell carcinoma in vitro and in vivo. After transfection of shRNA-targeting survivin, MTS assay showed that the survival rates of radiation groups were reduced with the prolongation of culture time (p < 0.05). In addition, shRNA-targeting survivin abrogated radiation-induced G2 phase arrest and amplified radiation-induced apoptosis. In vivo, shRNA transfection also sensitized tumor xenograft to radiotherapy. Radioresistance of laryngeal squamous cell carcinoma may be associated with increased expression of survivin, and survivin suppression may enhance the radiosensitivity of laryngeal squamous cell carcinoma.

Keywords

Laryngeal squamous cell carcinoma Radiosensitivity Survivin 

References

  1. 1.
    Shah, J. P., et al. (1997). Patterns of care for cancer of the larynx in the United States. Archives of Otolaryngology Head and Neck Surgery, 123(5), 475–483.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal, A., et al. (2009). Cancer statistics, 2009. CA A Cancer Journal for Clinicians, 59(4), 225–249.PubMedCrossRefGoogle Scholar
  3. 3.
    Zhao, X. D., et al. (2013). Overexpression of miR -155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3. PLoS ONE, 8(2), e56395.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer statistics, 2013. CA A Cancer Journal for Clinicians, 63(1), 11–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Bussink, J., van der Kogel, A. J., & Kaanders, J. H. (2008). Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. The Lancet Oncology, 9(3), 288–296.PubMedCrossRefGoogle Scholar
  6. 6.
    Kelly, R. J., et al. (2011). Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. Molecular Cancer, 10, 35.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Ambrosini, G., Adida, C., & Altieri, D. C. (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature Medicine, 3(8), 917–921.PubMedCrossRefGoogle Scholar
  8. 8.
    Adida, C., et al. (1998). Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet, 351(9106), 882–883.PubMedCrossRefGoogle Scholar
  9. 9.
    El Deeb, N. M., & Abdelzaher, E. (2014). Stem cell markers OCT4 and nestin in laryngeal squamous cell carcinoma and their relation to survivin expression. Pathology, Research and Practice, 210, 751–758.PubMedCrossRefGoogle Scholar
  10. 10.
    Marioni, G., et al. (2013). Relationship between anti-apoptotic proteins survivin and Bcl-2, and response to treatment in patients undergoing post-operative RT for laryngeal cancer: A pilot study. Journal of Oral Pathology and Medicine, 42(4), 339–344.PubMedCrossRefGoogle Scholar
  11. 11.
    Shen, J., et al. (2014). iRGD conjugated TPGS mediates codelivery of paclitaxel and survivin shRNA for the reversal of lung cancer resistance. Molecular Pharmaceutics, 11(8), 2579–2591.PubMedCrossRefGoogle Scholar
  12. 12.
    Qin, F. X., et al. (2011). Knockdown of NPM1 by RNA interference inhibits cells proliferation and induces apoptosis in leukemic cell line. International Journal of Medical Sciences, 8(4), 287–294.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Kami, K., et al. (2005). Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells. Surgery, 138(2), 299–305.PubMedCrossRefGoogle Scholar
  14. 14.
    Wang, J., et al. (2012). Knockdown of cyclin D1 inhibits proliferation, induces apoptosis, and attenuates the invasive capacity of human glioblastoma cells. Journal of Neuro-oncology, 106(3), 473–484.PubMedCrossRefGoogle Scholar
  15. 15.
    Ryan, B. M., O’Donovan, N., & Duffy, M. J. (2009). Survivin: A new target for anti-cancer therapy. Cancer Treatment Reviews, 35(7), 553–562.PubMedCrossRefGoogle Scholar
  16. 16.
    Mita, A. C., et al. (2008). Survivin: Key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clinical Cancer Research, 14(16), 5000–5005.PubMedCrossRefGoogle Scholar
  17. 17.
    Chen, X. M., et al. (2008). Suppression of survivin expression by short hairpin RNA induces apoptosis in human laryngeal carcinoma cells. ORL Journal of Oto-Rhino-Laryngology and Its Related Specialties, 70(3), 168–175.CrossRefGoogle Scholar
  18. 18.
    Lei, Y., et al. (2010). Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance. Molecular and Cellular Biochemistry, 344(1–2), 23–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Galloway, N. R., et al. (2009). Enhanced antitumor effect of combined gemcitabine and proton radiation in the treatment of pancreatic cancer. Pancreas, 38(7), 782–790.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Cao, C., et al. (2004). XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene, 23(42), 7047–7052.PubMedCrossRefGoogle Scholar
  21. 21.
    Asanuma, K., et al. (2000). Survivin as a radioresistance factor in pancreatic cancer. Japanese Journal of Cancer Research, 91(11), 1204–1209.PubMedCrossRefGoogle Scholar
  22. 22.
    Rodel, C., et al. (2003). Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities: Survivin as a radioresistance factor. International Journal of Radiation Oncology Biology Physics, 55(5), 1341–1347.CrossRefGoogle Scholar
  23. 23.
    Sun, H. B., Zheng, H. Y., & Yan, X. (2014). Survivin silencing enhances radiosensitivity in oral squamous cell carcinoma cell. European Review for Medical and Pharmacological Sciences, 18(18), 2678–2686.PubMedGoogle Scholar
  24. 24.
    Song, H., et al. (2008). Survivin gene RNA interference inhibits proliferation, induces apoptosis, and enhances radiosensitivity in HeLa cells. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 136(1), 83–89.PubMedCrossRefGoogle Scholar
  25. 25.
    Chen, X. Q., et al. (2012). Effects and mechanism of downregulation of survivin expression by RNA interference on proliferation and apoptosis of lung cancer cells. Molecular Medicine Reports, 5(4), 917–922.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Liu, W., et al. (2013). siRNA targeting survivin inhibits the growth and enhances the chemosensitivity of hepatocellular carcinoma cells. Oncology Reports, 29(3), 1183–1188.PubMedGoogle Scholar
  27. 27.
    Wenying, Z., et al. (2012). Survivin siRNA inhibits gastric cancer in nude mice. Cell Biochemistry and Biophysics, 62(2), 337–341.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of OtorhinolaryngologyRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  2. 2.Department of PediatricsTaihe Hospital Affiliated with Hubei University of MedicineShiyanPeople’s Republic of China
  3. 3.Department of OncologyTaihe Hospital Affiliated with Hubei University of MedicineShiyanPeople’s Republic of China

Personalised recommendations