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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
October 2013 Volume 43 Issue 4

Full Size Image

Cover Legend PDF

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
October 2013 Volume 43 Issue 4

Full Size Image

Cover Legend PDF

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

RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity

  • Authors:
    • Wenxuan Zhang
    • Lina Xing
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, P.R. China
  • Pages: 1228-1234
    |
    Published online on: August 6, 2013
       https://doi.org/10.3892/ijo.2013.2051
  • 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

Telomerase activity (TA) is reactivated in more than 90% of all human malignant tumors and normal somatic cells that lack TA. Thus, human TERT (hTERT) is a promising target in malignant tumor treatment. RNA interference is a powerful tool for gene silencing. In this study, we constructed siRNA#1-4 to knock down hTERT. All siRNAs were able to downregulate hTERT differently and we chose siRNA#3 (most effectively) in the following experiments. We studied the effects on cell proliferation, cell cycle, cell apoptosis and radiosensitivity using SiHa cells. Our results showed that siRNA#3 was able to silence hTERT gene effectively. The silencing of hTERT could induce immediate growth arrest, enhance the S phase in cell cycle study and lead to early apoptosis in human cervical cancer cells (SiHa). In clonogenic assays, we used multitarget-single hit and linear-quadratic models to assess the radiosensitivity after knockdown of hTERT. All results of parameters (D0, Dq, α, β) indicated that downregulation of hTERT enhanced radiosensitivity in SiHa cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1. 

Collins K and Mitchell JR: Telomerase in the human organism. Oncogene. 21:564–579. 2002. View Article : Google Scholar : PubMed/NCBI

2. 

Blackburn EH: Swiching and signaling at the telomere. Cell. 106:661–673. 2001. View Article : Google Scholar : PubMed/NCBI

3. 

De Lange T: How telomeres solve the end-protection problem. Science. 326:948–952. 2009.PubMed/NCBI

4. 

Satra M, Tsougos I, Papanikolaou V, Theodorou K, Kappas C and Tsezou A: Correlation between radiation-induced telomerase activity and human telomerase reverse transcriptase mRNA expression in HeLa cells. Int J Radiat Biol. 6:401–409. 2009.PubMed/NCBI

5. 

Qi DL, Ohhira T, Fujisaki C, et al: Identification of PITX1 as a TERT suppressor gene located on human chromosome. Mol Cell Biol. 31:1624–1636. 2011. View Article : Google Scholar : PubMed/NCBI

6. 

He X, Qiao Q, Ge N, Nan J, Shen S, Wang Z, Yang Y and Bao G: Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population. BMC Cancer. 10:312–321. 2010. View Article : Google Scholar : PubMed/NCBI

7. 

Kyo S, Takakura M, Fujiwara T and Inoue M: Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci. 99:1528–1538. 2008. View Article : Google Scholar : PubMed/NCBI

8. 

Gomez-Millan J, Goldblatt EM, Gryaznov SM, Mendonca MS and Herbert BS: Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. Int J Radiat Oncol Biol Phys. 67:897–905. 2007. View Article : Google Scholar : PubMed/NCBI

9. 

Liu X, Huang H, Wang J, Wang C, Wang M, Zhang B and Pan C: Dendrimers-delivered short hairpin RNA targeting hTERT inhibits oral cancer cell growth in vitro and in vivo. Biochem Pharmacol. 82:17–23. 2011. View Article : Google Scholar : PubMed/NCBI

10. 

Ram R, Uziel O, Eldan O, et al: Ionizing radiation upregulates telomerase activity in cancer cell lines by post-translational mechanism via ras/phosphatidylinositol 3-kinase/akt pathway. Clin Cancer Res. 15:914–923. 2009. View Article : Google Scholar : PubMed/NCBI

11. 

Liu X, Jiang L, Wang A, Yu J, Shi F and Zhou X: MicroRNA-138 suppresses invasion and promotes apoptosis in head and neck squamous cell carcinoma cell lines. Cancer Lett. 28:217–222. 2009. View Article : Google Scholar : PubMed/NCBI

12. 

Dykxhoorn DM, Palliser D and Lieberman J: The silent treatment: siRNAs as small molecule drugs. Gene Ther. 13:541–552. 2006. View Article : Google Scholar : PubMed/NCBI

13. 

Gazzaniga P, Gradilone A, Giuliani L, et al: Expression and prognostic significance of Livin, Survivin and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol. 14:85–90. 2003. View Article : Google Scholar

14. 

Cech TR: Beginning to understand the end of the chromosome. Cell. 116:273–279. 2004. View Article : Google Scholar : PubMed/NCBI

15. 

Luo Y, Yi Y and Yao Z: Growth arrest in ovarian cancer cells by hTERT inhibition short-hairpin RNA targeting human telomerase reverse transcriptase induces immediate growth inhibition but not necessarily induces apoptosis in ovarian cancer cells. Cancer Invest. 27:960–970. 2009. View Article : Google Scholar

16. 

Zheng JN, Pei DS, Sun FH, et al: Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene. Cancer Biol Ther. 8:1–8. 2009. View Article : Google Scholar : PubMed/NCBI

17. 

Wang R, Lin F, Wang X, et al: The therapeutic potential of surviving promoter-driven siRNA on suppressing tumor growth and enhancing radiosensitivity of human cervical carcinoma cells via downregulating hTERT gene expression. Cancer Biol Ther. 6:1295–1301. 2007. View Article : Google Scholar

18. 

Hauguel T and Bunz F: Haploinsufficiency of hTERT leads to telomere dysfunction and radiosensitivity in human cancer cells. Cancer Biol Ther. 2:679–684. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Emastman A: Cell cycle checkpoints and their impact on anticancer therapeutic strategies. J Cell Biochem. 91:223–231. 2004. View Article : Google Scholar : PubMed/NCBI

20. 

Tomlinson RL, Ziegler TD, Supakorndej T, et al: Cell cycle-regulated trafficking of human telomerase to telomeres. Mol Biol Cell. 17:955–965. 2006. View Article : Google Scholar : PubMed/NCBI

21. 

Abreu E, Aritonovska E, Reichenbach P, et al: TIN2-tethered TPP1 recruits human telomerase to telomere in vivo. Mol Cell Biol. 30:2971–2982. 2010. View Article : Google Scholar : PubMed/NCBI

22. 

Zhao Y, Abreu E, Kim J, et al: Progressive and distributive extention of human telomeres by telomerase under homeostatic and nonequilibrium conditions. Mol Cell. 42:297–307. 2011. View Article : Google Scholar : PubMed/NCBI

23. 

Kurvinen K, Rantanen V, Syrjänen S and Johansson B: Radiation-induced effects on telomerase in gynecological cancer cell lines with different radiosensitivity and repair capacity. Int J Radiat Biol. 82:859–867. 2006. View Article : Google Scholar : PubMed/NCBI

24. 

Nedime S, Rikke C, Jesper G, et al: Ectopically hTERT expressing adult human mesenchymal stem cells are less radio-sensitive than their telomerase negative counterpart. Exp Cell Res. 313:1056–1067. 2007. View Article : Google Scholar

25. 

Goytisolo FA, Samper E, Martín-Caballero J, et al: Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals. J Exp Med. 192:1625–1636. 2000. View Article : Google Scholar : PubMed/NCBI

26. 

Natarajan M, Mohan S, Konopinski R, Aotto R, et al: Induced telomerase activity in primary aortic endothelial cells by low-let γ-radiation is mediated through NF-κB activation. Br J Radiol. 81:711–720. 2008.PubMed/NCBI

27. 

Natarajan A, Jamunarani V, Rakhesh M, et al: Curcumin regulates low-linear energy transfer γ-radiation-induced NF-κB-dependent telomerase activity in human neuroblastoma cells. Int J Radiat Oncol Biol Phys. 79:1206–1215. 2011.PubMed/NCBI

28. 

Papanikolaou V, Iliopoulos D, Dimou I, et al: The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells. Int J Oncol. 35:1141–1149. 2009.PubMed/NCBI

29. 

Hideaki N: hTERT-immortalized cells useful for analyzing effects of low-dose-rate radiation on human cells. J Radiat Res. 49:9–15. 2008. View Article : Google Scholar : PubMed/NCBI

30. 

Castella M, Puerto S, Creus A, et al: Telomere length modulateds human radiation sensitivity in vitro. Toxicol Lett. 172:29–36. 2007. View Article : Google Scholar : PubMed/NCBI

31. 

Weng D, Cunin MC, Song B, et al: Radiosensitization of mammary carcinoma cells by telomere homolog oligonucleotide pretreatment. Breast Cancer Res. 12:R712010. View Article : Google Scholar : PubMed/NCBI

32. 

Drissi R, Wu J, Hu Y, et al: Telomere shorting alters the kinetics of the DNA damage response after ionizing radiation in human cells. Cancer Prev Res. 4:1973–1981. 2011. View Article : Google Scholar : PubMed/NCBI

33. 

Guilleret I and Benhattar J: Demethylation of the human telomerase catalytic subunit (hTERT) gene promoter reduced hTERT expression and telomerase activity and shortened telomeres. Exp Cell Res. 289:326–334. 2003. View Article : Google Scholar

34. 

Ji XM, Xie CH, Fang MH, et al: Efficient inhibition of human telomerase activity by antisense oligonucotides sensitizes cancer cells to radiotherapy. Acta Pharmacol Sin. 27:1185–1191. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang W and Xing L: RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity. Int J Oncol 43: 1228-1234, 2013.
APA
Zhang, W., & Xing, L. (2013). RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity. International Journal of Oncology, 43, 1228-1234. https://doi.org/10.3892/ijo.2013.2051
MLA
Zhang, W., Xing, L."RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity". International Journal of Oncology 43.4 (2013): 1228-1234.
Chicago
Zhang, W., Xing, L."RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity". International Journal of Oncology 43, no. 4 (2013): 1228-1234. https://doi.org/10.3892/ijo.2013.2051
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W and Xing L: RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity. Int J Oncol 43: 1228-1234, 2013.
APA
Zhang, W., & Xing, L. (2013). RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity. International Journal of Oncology, 43, 1228-1234. https://doi.org/10.3892/ijo.2013.2051
MLA
Zhang, W., Xing, L."RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity". International Journal of Oncology 43.4 (2013): 1228-1234.
Chicago
Zhang, W., Xing, L."RNAi gene therapy of SiHa cells via targeting human TERT induces growth inhibition and enhances radiosensitivity". International Journal of Oncology 43, no. 4 (2013): 1228-1234. https://doi.org/10.3892/ijo.2013.2051
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