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
December-2016 Volume 12 Issue 6

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
December-2016 Volume 12 Issue 6

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

RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy

  • Authors:
    • Jing Gan
    • Fangfang Wang
    • Dezhi Mu
    • Yi Qu
    • Rong Luo
    • Qiu Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4515-4523
    |
    Published online on: October 14, 2016
       https://doi.org/10.3892/ol.2016.5261
  • 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

Clinically, temozolomide (TMZ) is widely used in glioblastoma (GBM) treatment. However, the toxicity of TMZ may influence the quality of patient life. Thus, novel treatment options for sensitizing GBM cells to TMZ chemotherapy are necessary. Aurora‑A is widely expressed in GBM and correlated with poor prognosis. It has been proven to be an effective target for gene therapy and chemotherapy. In the present study, short hairpin (sh)RNA targeting Aurora‑A was employed to knockdown Aurora‑A expression in GBM cells. Cell Counting Kit‑8 assays, flow cytometry, colony formation assays, invasion assays and tube formation assays were used to determine the effects of Aurora‑A knockdown when combined with TMZ treatment. A U251 subcutaneous cancer model was established to evaluate the efficacy of combined therapy. The results of the present study indicated that the proliferation, colony formation, invasion and angiogenesis of GBM cells were significantly inhibited by combined therapy when compared with TMZ treatment alone. In vivo results demonstrated that knockdown of Aurora‑A significantly (P=0.0084) sensitizes GBM cells to TMZ chemotherapy. The results of the present study demonstrated that knockdown of Aurora‑A in GBM cells enhances TMZ sensitivity in vitro and in vivo. Therefore, Aurora‑A knockdown may be a novel treatment option for decreasing TMZ toxicity and improving patient quality of life.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Sathornsumetee S and Rich JN: New treatment strategies for malignant gliomas. Expert Rev Anticancer Ther. 6:1087–1104. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Mrugala MM and Chamberlain MC: Mechanisms of disease: Temozolomide and glioblastoma-look to the future. Nat Clin Pract Oncol. 5:476–486. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Friedman HS, Kerby T and Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 6:2585–2597. 2000.PubMed/NCBI

4 

Osoba D, Brada M, Yung WK and Prados M: Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme. J Clin Oncol. 18:1481–1491. 2000.PubMed/NCBI

5 

Margison GP, Santibáñez Koref MF and Povey AC: Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine. Mutagenesis. 17:483–487. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Hirose Y, Berger MS and Pieper RO: p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Cancer Res. 61:1957–1963. 2001.PubMed/NCBI

7 

Quiros S, Roos WP and Kaina B: Processing of O6-methylguanine into DNA double-strand breaks requires two rounds of replication whereas apoptosis is also induced in subsequent cell cycles. Cell Cycle. 9:168–178. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Ahluwalia MS, Xie H, Dahiya S, Hashemi-Sadraei N, Schiff D, Fisher PG, Chamberlain MC, Pannullo S, Newton HB, Brewer C, et al: Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: A phase II multicenter study. J Neurooncol. 122:111–119. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Taphoorn MJ, Henriksson R, Bottomley A, Cloughesy T, Wick W, Mason WP, Saran F, Nishikawa R, Hilton M, Theodore-Oklota C, et al: Health-Related quality of life in a randomized phase III study of bevacizumab, temozolomide, and radiotherapy in newly diagnosed glioblastoma. J Clin Oncol. 33:2166–2175. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Marumoto T, Honda S, Hara T, Nitta M, Hirota T, Kohmura E and Saya H: Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem. 278:51786–51795. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Seki A, Coppinger JA, Jang CY, Yates JR and Fang G: Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry. Science. 320:1655–1658. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, Brinkley BR and Sen S: Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nature Genet. 20:189–193. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Sen S, Zhou H and White RA: A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene. 14:2195–2200. 1997. View Article : Google Scholar : PubMed/NCBI

14 

Van Brocklyn JR, Wojton J, Meisen WH, Kellough DA, Ecsedy JA, Kaur B and Lehman NL: Aurora-A inhibition offers a novel therapy effective against intracranial glioblastoma. Cancer Res. 74:5364–5370. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Yang H, Ou CC, Feldman RI, Nicosia SV, Kruk PA and Cheng JQ: Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells. Cancer Res. 64:463–467. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA and Sen S: Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet. 36:55–62. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Qin L, Tong T, Song Y, Xue L, Fan F and Zhan Q: Aurora-A interacts with Cyclin B1 and enhances its stability. Cancer Lett. 275:77–85. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Sasayama T, Marumoto T, Kunitoku N, Zhang D, Tamaki N, Kohmura E, Saya H and Hirota T: Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1. Genes Cells. 10:627–638. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Yang S, He S, Zhou X, Liu M, Zhu H, Wang Y, Zhang W, Yan S, Quan L, Bai J and Xu N: Suppression of Aurora-A oncogenic potential by c-Myc downregulation. Exp Mol Med. 42:759–767. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Carol H, Boehm I, Reynolds CP, Kang MH, Maris JM, Morton CL, Gorlick R, Kolb EA, Keir ST, Wu J, et al: Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer. Cancer Chemother Pharmacol. 68:1291–1304. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Huck JJ, Zhang M, McDonald A, Bowman D, Hoar KM, Stringer B, Ecsedy J, Manfredi MG and Hyer ML: MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo. Mol Cancer Res. 8:373–384. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, Ohmura N, Marumoto T, Saya H and Horii A: RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res. 65:2899–2905. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Dai L, Cui X, Zhang X, Cheng L, Liu Y, Yang Y, Fan P, Wang Q, Lin Y, Zhang J, et al: SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin. Nat Commun. 7:19962016. View Article : Google Scholar

24 

Dai L, Cheng L, Zhang X, Jiang Q, Zhang S, Wang S, Li Y, Chen X, Du T, Yang Y, et al: Plasmid-based STAT3-siRNA efficiently inhibits breast tumor growth and metastasis in mice. Neoplasma. 58:538–547. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Wang W, Dai LX, Zhang S, Yang Y, Yan N, Fan P, Dai L, Tian HW, Cheng L, Zhang XM, et al: Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo. Neoplasma. 60:274–283. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Cammareri P, Scopelliti A, Todaro M, Eterno V, Francescangeli F, Moyer MP, Agrusa A, Dieli F, Zeuner A and Stassi G: Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res. 70:4655–4665. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, Mehta MP and Gilbert MR: Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 26:4189–4199. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Jiang Z, Pore N, Cerniglia GJ, Mick R, Georgescu MM, Bernhard EJ, Hahn SM, Gupta AK and Maity A: Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir. Cancer Res. 67:4467–4473. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Woo SR, Ham Y, Kang W, Yang H, Kim S, Jin J, Joo KM and Nam DH: KML001, a telomere-targeting drug, sensitizes glioblastoma cells to temozolomide chemotherapy and radiotherapy through DNA damage and apoptosis. Biomed Res Int. 2014:7474152014. View Article : Google Scholar : PubMed/NCBI

30 

Goellner EM, Grimme B, Brown AR, Lin YC, Wang XH, Sugrue KF, Mitchell L, Trivedi RN, Tang JB and Sobol RW: Overcoming temozolomide resistance in glioblastoma via dual inhibition of NAD+ biosynthesis and base excision repair. Cancer Res. 71:2308–2317. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Park I, Mukherjee J, Ito M, Chaumeil MM, Jalbert LE, Gaensler K, Ronen SM, Nelson SJ and Pieper RO: Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells. Cancer Res. 74:7115–7124. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gan J, Wang F, Mu D, Qu Y, Luo R and Wang Q: RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy. Oncol Lett 12: 4515-4523, 2016.
APA
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., & Wang, Q. (2016). RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy. Oncology Letters, 12, 4515-4523. https://doi.org/10.3892/ol.2016.5261
MLA
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., Wang, Q."RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy". Oncology Letters 12.6 (2016): 4515-4523.
Chicago
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., Wang, Q."RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy". Oncology Letters 12, no. 6 (2016): 4515-4523. https://doi.org/10.3892/ol.2016.5261
Copy and paste a formatted citation
x
Spandidos Publications style
Gan J, Wang F, Mu D, Qu Y, Luo R and Wang Q: RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy. Oncol Lett 12: 4515-4523, 2016.
APA
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., & Wang, Q. (2016). RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy. Oncology Letters, 12, 4515-4523. https://doi.org/10.3892/ol.2016.5261
MLA
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., Wang, Q."RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy". Oncology Letters 12.6 (2016): 4515-4523.
Chicago
Gan, J., Wang, F., Mu, D., Qu, Y., Luo, R., Wang, Q."RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy". Oncology Letters 12, no. 6 (2016): 4515-4523. https://doi.org/10.3892/ol.2016.5261
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