Skip to main content Accessibility help

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

  • X Zhou (a1), Y Yuan (a2), J Song (a2) (a3), W Chen (a4), J Li (a1), L Ye (a1), X Meng (a5) and D Xia (a6)...



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.


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.


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.


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.


Corresponding author

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:


Hide All
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;8597
2Ayan, I, Kaytan, E, Ayan, N. Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 2003;4:1321
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):192200
4Hortobagyi, GN. Trastuzumab in the treatment of breast cancer. N Engl J Med 2005;353:1734–6
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;54:125–32
6Werner, H, Roberts, CT Jr. The IGFI receptor gene: a molecular target for disrupted transcription factors. Genes Chromosomes Cancer 2003;36:113–20
7Vincent, AM, Feldman, EL. Control of cell survival by IGF signaling pathways. Growth Horm IGF Res 2002;12:193–7
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):19
9Hannon, GJ. RNA interference. Nature 2002;418:244–51
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;324:1173–8
11Montgomery, MK. RNA interference: historical overview and significance. Methods Mol Biol 2004;265:321
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;391:806–11
13Paddison, PJ, Caudy, AA, Bernstein, E, Hannon, GJ, Conklin, DS. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 2002;16:948–58
14Brummelkamp, TR, Bernards, R, Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002;296:550–3
15Zhang, DL, Zhang, YT, Yin, JJ, Zhao, BL. Oral administration of crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils. J Neurochem 2004;90:211–19
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;106:397405
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;71:1265–75
18Pardridge, WM. Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 2004;4:1103–13
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;53:315–25
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;49:427–37



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed