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Dual silencing of epidermal growth factor and insulin-like growth factor 1 receptors significantly limits growth of nasopharyngeal carcinoma in nude mice

Published online by Cambridge University Press:  01 May 2008

X Zhou ,
Y Yuan ,
J Song ,
W Chen ,
J Li ,
L Ye ,
X Meng  and
D Xia
X Zhou
Affiliation:
Department of Otolaryngology-Head & Neck Surgery, Zhongnan Hospital of Wuhan University, China
Y Yuan*
Affiliation:
Department of Anatomy, Wuhan University School of Medicine, China
J Song
Affiliation:
Department of Anatomy, Wuhan University School of Medicine, China Key Laboratory of Allergy and Immune-related Diseases and the Center for Medical Research, Wuhan University, China
W Chen
Affiliation:
Experimental Animal Centre, Zhongnan Hospital of Wuhan University, China
J Li
Affiliation:
Department of Otolaryngology-Head & Neck Surgery, Zhongnan Hospital of Wuhan University, China
L Ye
Affiliation:
Department of Otolaryngology-Head & Neck Surgery, Zhongnan Hospital of Wuhan University, China
X Meng
Affiliation:
Department of Forensic Medicine, Wuhan University School of Medicine, China
D Xia
Affiliation:
Department of Pathology, Wuhan University School of Medicine, China
*
Address for correspondence: Prof Yulin Yuan, Department of Anatomy, Wuhan University School of Medicine, 135 Donghu Road, Wuhan, Hubei 430071 PRChina. Fax:  +86 27 87307966 E-mail: [email protected]
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Abstract

Objective:

We examined the effects of dual silencing of epidermal growth factor and insulin-like growth factor 1 receptors on the growth of nasopharyngeal carcinoma in nude mice; we also assessed potential side effects in these animals.

Methods:

Short hairpin ribonucleic acid expression vectors targeting epidermal growth factor and insulin-like growth factor 1 receptors were constructed. Short hairpin ribonucleic acid plasmids targeting one or both receptors were transfected into human nasopharyngeal carcinoma cells in nude mice. We then assessed epidermal growth factor receptor and insulin-like growth factor 1 receptor expression and also cellular apoptosis. Peripheral blood was collected and subjected to haematological and biochemical analysis.

Results:

The findings demonstrated that transfection with dual plasmids (targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor) resulted in tumour cell growth inhibition of 84.78 per cent, and a significant increase in the number of necrotic and apoptotic cells, compared with single plasmid treatment. The short hairpin ribonucleic acid had no significant side effects on the heart, liver, kidney, spleen or blood system in this experimental model.

Conclusion:

These results indicate that, in nude mice, dual silencing of both epidermal growth factor and insulin-like growth factor 1 receptors results in more apoptosis and greater nasopharyngeal cancer cell growth inhibition, compared with silencing of either epidermal growth factor receptor alone or insulin-like growth factor 1 receptor alone. This occurred without significant side effects in the experimental animals.

Keywords

Small Hairpin RNAEGF ReceptorIGF-1 ReceptorNasopharynx NeoplasmsCarcinoma
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 123 , Issue 2 , February 2009 , pp. 208 - 222
Copyright
Copyright © JLO (1984) Limited 2008

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References

1Chan, J, Plich, BZ, Kuo, TT. Nasopharyngeal carcinoma. In: Barnes, L, Eveson, JW, Reichart, P, Sidransky, D, eds. WHO Health Organization Classification of Tumors – Pathology & Genetics: Head and Neck Tumors. Lyon: IARC Press, 2005;85–97Google Scholar
2Ayan, I, Kaytan, E, Ayan, N. Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 2003;4:13–21CrossRefGoogle ScholarPubMed
3Yulin, Yuan, Xuhong, Zhou, Jian, Song, Xiaoping, Qiu, Jun, Li, Linfeng, Ye, Xiaoping, Meng, Dong, Xia. Expressions and clinical significances of EGF and IGF-1 receptors in nasopharyngeal carcinoma. The Annals of Otology, Rhinology & Laryngology 2008;117 (3):192–200Google Scholar
4Hortobagyi, GN. Trastuzumab in the treatment of breast cancer. N Engl J Med 2005;353:1734–6CrossRefGoogle ScholarPubMed
5Ward, CW, Garrett, TP, McKern, NM, Lou, M, Cosgrove, LJ, Sparrow, LG et al. The three dimensional structure of the type I insulin-like growth factor receptor. Mol Pathol 2001;54:125–32CrossRefGoogle ScholarPubMed
6Werner, H, Roberts, CT Jr. The IGFI receptor gene: a molecular target for disrupted transcription factors. Genes Chromosomes Cancer 2003;36:113–20CrossRefGoogle ScholarPubMed
7Vincent, AM, Feldman, EL. Control of cell survival by IGF signaling pathways. Growth Horm IGF Res 2002;12:193–7CrossRefGoogle ScholarPubMed
8Yuan, Y-L, Zhou, X-H, Song, Jian, Qiu, X-P, Li, Jun, Yed, L-F. Dual silencing of type 1 insulin-like growth factor and epidermal growth factor receptors to induce apoptosis of nasopharyngeal cancer cells. J Laryngol Otol, 2007; Oct 2; 121 (10):1–9Google Scholar
9Hannon, GJ. RNA interference. Nature 2002;418:244–51CrossRefGoogle ScholarPubMed
10Liu, XD, Ma, SM, Liu, Y, Liu, SZ, Sehon, A. Short hairpin RNA and retroviral vector-mediated silencing of p53 in mammalian cells. Biochem Biophys Res Commun 2004;324:1173–8CrossRefGoogle ScholarPubMed
11Montgomery, MK. RNA interference: historical overview and significance. Methods Mol Biol 2004;265:3–21Google ScholarPubMed
12Fire, A, Xu, S, Montgomery, MK, Kostas, SA, Driver, SE, Mello, CC et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998;391:806–11CrossRefGoogle ScholarPubMed
13Paddison, PJ, Caudy, AA, Bernstein, E, Hannon, GJ, Conklin, DS. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 2002;16:948–58CrossRefGoogle ScholarPubMed
14Brummelkamp, TR, Bernards, R, Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002;296:550–3CrossRefGoogle ScholarPubMed
15Zhang, DL, Zhang, YT, Yin, JJ, Zhao, BL. Oral administration of crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils. J Neurochem 2004;90:211–19CrossRefGoogle ScholarPubMed
16Zhou, XD, Yu, JP, Liu, J, Luo, HS, Chen, HX, Chen, Y-X et al. Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma. Clin Sci (Lond) 2004;106:397–405CrossRefGoogle ScholarPubMed
17Bai, L, Zhu, R, Chen, Z, Gao, L, Zhang, X, Wang, X et al. Potential of short hairpin RNA targeting epidermal growth factor receptor in growth and sensitivity to drugs of human lung adenocarcinoma cells. Biochem Pharmacol 2006;71:1265–75CrossRefGoogle ScholarPubMed
18Pardridge, WM. Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 2004;4:1103–13CrossRefGoogle ScholarPubMed
19Oldak, M, Malejczyk, J. Signal transduction mechanisms induced by epidermal growth factor receptor (EGFR) and their role in apoptosis regulation. Postepy Hig Med Dosw 1999;53:315–25Google ScholarPubMed
20Harari, PM, Huang, SM. Head and neck cancer as a clinical model for molecular targeting of therapy: Combining EGFR blockade with radiation. Int J Radiat Oncol Biol Phys 2001;49:427–37CrossRefGoogle ScholarPubMed