Antisense oligonucleotides targeting human telomerase mRNA increases the radiosensitivity of nasopharyngeal carcinoma cells

Yu,Change; Yu,Ying; Xu,Zumin; Li,Haiwen; Yang,Dongyan; Xiang,Mei; Zuo,Yufang; Li,Shuhui; Chen,Zihong; Yu,Zhonghua

doi:10.3892/mmr.2014.3105

April-2015 Volume 11 Issue 4

Full Size Image

Journals

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 is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

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

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

April-2015 Volume 11 Issue 4

Full Size Image

Article

Antisense oligonucleotides targeting human telomerase mRNA increases the radiosensitivity of nasopharyngeal carcinoma cells

Authors:
- Change Yu
- Ying Yu
- Zumin Xu
- Haiwen Li
- Dongyan Yang
- Mei Xiang
- Yufang Zuo
- Shuhui Li
- Zihong Chen
- Zhonghua Yu
View Affiliations / Copyright

Affiliations: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524000, P.R. China
Pages: 2825-2830
|
Published online on: December 17, 2014

https://doi.org/10.3892/mmr.2014.3105
Expand metrics +

Abstract

Nasopharyngeal carcinoma (NPC) is associated with a high incidence rate in South China and is predominantly treated with radiotherapy; however, the survival rate remains low. The therapeutic effects of radiation and chemotherapy may be enhanced when combined with anti‑sense oligonucleotides targeting human telomerase RNA (hTR ASODN). However, the influence of hTR ASODN on the anti‑tumor effects of radiation in NPC remain unknown. The present study investigated the effects of hTR ASODN on the proliferation and radiosensitivity of NPC cells, and further explored the underlying mechanisms. hTR ASODN significantly inhibited the proliferation and decreased the telomere length of CNE‑2 human NPC cells. Furthermore, combined treatment of hTR ASODN with radiation significantly enhanced anti‑tumor efficacy. The apoptotic rate and cleavage of caspase 9 were increased in the cells treated with the combined therapy, as compared with the cells treated with hTR ASODN or radiotherapy alone. In conclusion, these results suggest that hTR ASODN may inhibit the proliferation of NPC cells and enhance the anti‑tumor effects of radiation by inducing cell apoptosis. Therefore hTR ASODN may be a potential adjuvant agent for the treatment of NPC combined with radiation therapy, and these findings are of translational importance.

View Figures

View References

1	Wei WI and Sham JS: Nasopharyngeal carcinoma. Lancet. 365:2041–2054. 2005. View Article : Google Scholar : PubMed/NCBI
2	Yu MC and Yuan JM: Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 12:421–429. 2002. View Article : Google Scholar : PubMed/NCBI
3	Feng BJ, Huang W, Shugart YY, et al: Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nat Genet. 31:395–399. 2002.PubMed/NCBI
4	Lee N, Xia P, Quivey JM, et al: Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 53:12–22. 2002. View Article : Google Scholar : PubMed/NCBI
5	Yang GD, Huang TJ, Peng LX, et al: Epstein-Barr Virus_Encoded LMP1 upregulates microRNA-21 to promote the resistance of nasopharyngeal carcinoma cells to cisplatin-induced Apoptosis by suppressing PDCD4 and Fas-L. PLoS One. 8:e783552013. View Article : Google Scholar : PubMed/NCBI
6	Ruden M and Puri N: Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev. 39:444–456. 2013. View Article : Google Scholar
7	Ouellette MM, Wright WE and Shay JW: Targeting telomerase-expressing cancer cells. J Cell Mol Med. 15:1433–1442. 2011. View Article : Google Scholar : PubMed/NCBI
8	Ruden M and Puri N: Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev. 39:444–456. 2013. View Article : Google Scholar
9	Röth A, Harley CB and Baerlocher GM: Imetelstat (GRN163L) - telomerase-based cancer therapy. Recent Results Cancer Res. 184:221–234. 2010. View Article : Google Scholar
10	Shay JW and Keith WN: Targeting telomerase for cancer therapeutics. Br J Cancer. 98:677–683. 2008. View Article : Google Scholar : PubMed/NCBI
11	Xu Q, Zhang Z, Zhang P and Chen W: Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma. BMC Cancer. 8:1592008. View Article : Google Scholar : PubMed/NCBI
12	Goldblatt EM, Gentry ER, Fox MJ, Gryaznov SM, Shen C and Herbert BS: The telomerase template antagonist GRN163L alters MDA-MB-231 breast cancer cell morphology, inhibits growth, and augments the effects of paclitaxel. Mol Cancer Ther. 8:2027–2035. 2009. View Article : Google Scholar : PubMed/NCBI
13	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
14	Xu Z, Fang S, Zuo Y, et al: Combination of pigment epithelium-derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis. Cancer Sci. 102:1789–1798. 2011. View Article : Google Scholar : PubMed/NCBI
15	Blackburn EH: Switching and signaling at the telomere. Cell. 106:661–673. 2001. View Article : Google Scholar : PubMed/NCBI
16	Kyo S and Inoue M: Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy? Oncogene. 21:688–697. 2002. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Zhang H, Zhai Y, et al: A functional tandem-repeats polymorphism in the downstream of TERT is associated with the risk of nasopharyngeal carcinoma in Chinese population. BMC Med. 9:1062011. View Article : Google Scholar : PubMed/NCBI
18	Wang Y, Duan HG, Chen SM, Xiao BK, Cheng J and Tao ZZ: Effect of RNA interference targeting human telomerase reverse transcriptase on telomerase and its related protein expression in nasopharyngeal carcinoma cells. J Laryngol Otol. 121:476–482. 2007. View Article : Google Scholar
19	Zhang SZ, Huang PC, Xu Y, Chen J and Cai KR: Effects of telomerase sense and antisense oligodeoxynucleotides on growth and differentiation of nasopharyngeal carcinoma cells. Ai Zheng. 21:493–497. 2002.(In Chinese). PubMed/NCBI
20	Marian CO, Cho SK, McEllin BM, et al: The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth. Clin Cancer Res. 16:154–163. 2010. View Article : Google Scholar : PubMed/NCBI
21	Wang X, Liu Y, Chow LS, et al: Regulation of telomerase activity by gamma-radiation in nasopharyngeal carcinoma cells. Anticancer Res. 20:433–437. 2000.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Antisense oligonucleotides targeting human telomerase mRNA increases the radiosensitivity of nasopharyngeal carcinoma cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Related Articles