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Dual silencing of type 1 insulin-like growth factor and epidermal growth factor receptors to induce apoptosis of nasopharyngeal cancer cells

Published online by Cambridge University Press:  02 October 2007

Y-L Yuan ,
X-H Zhou ,
Jian Song ,
X-P Qiu ,
Jun Li  and
L-F Ye
Y-L Yuan
Affiliation:
Department of Anatomy, Wuhan University School of Medicine, Wuhan, PR China
X-H Zhou
Affiliation:
Department of Otolaryngology–Head & Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan, PR China
Jian Song*
Affiliation:
Department of Otolaryngology–Head & Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan, PR China
X-P Qiu
Affiliation:
Medical Institute of Virus Research, Wuhan University, Wuhan, PR China
Jun Li
Affiliation:
Department of Otolaryngology–Head & Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan, PR China
L-F Ye
Affiliation:
Department of Otolaryngology–Head & Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan, PR China
*
Address for correspondence: Dr Jian Song, Department of Anatomy, Wuhan University School of Medicine, Wuhan 430071, PR China E-mail: y030612_030912_04021@126.com
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Abstract

Objective:

The epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (type 1 IGF receptor or IGF1R) have played an important role in the growth and apoptosis of cancer. The RNA interference (RNAi) technique can suppress gene expression, but the effects of dual silencing of EGFR and type 1 IGF receptor have not been well understood.

Methods:

pU6-EGFR-shRNA-1, pU6-EGFR-shRNA-2, pU6-IGF1R-shRNA-1 and pU6-IGF-1R-shRNA-2 plasimd vectors were transfected to the nasopharyngeal cancer cells. Seven groups were selected for the study. The protein and downstream protein expression were assessed by Western blot. Apoptosis was determined via flow cytometry. Meanwhile, chemosensitivity of nasopharyngeal cancer cell lines transfeced to chemotherapeutic drugs were carried out by MTT.

Results:

In dual silencing of EGFR and IGF-1R, the protein expression much more was decreased than single silencing of EGFR or IGF-1R, but the cell apoptosis much more is increased than single silencing EGFR or IGF-1R. Dual silencing of EGFR and IGF-1R enhanced chemosensitivity to anticancer drugs, compared with single silencing of EGFR or IGF-1R.

Conclusion:

Dual silencing of EGFR and IGF-1R are capable of suppressing EGFR and IGF-1R expression of the nasopharyngeal cancer cell and can promote apoptosis and increase the cell sensitivity of anticancer drug. The dual silencing of genes RNAi technique is significantly better than a single gene.

Keywords

RNA interferenceDual silencing genesNasopharyngeal cancerEpidermal growth factor receptorType 1 insulin-like growth factor receptor
Type
Main Article
Information
The Journal of Laryngology & Otology , Volume 122 , Issue 9 , September 2008 , pp. 952 - 960
Copyright
Copyright © JLO (1984) Limited 2007

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References

1 Parkin, DM, Pisani, P, Ferlay, J. Global cancer statistics. CA Cancer J Clin 1999;49:33–64CrossRefGoogle ScholarPubMed
2 Su, CK, Wang, CC. Prognostic value of Chinese race in nasopharyngeal cancer. Int J Radiat Oncol Biol Phys 2002;54:752–8CrossRefGoogle ScholarPubMed
3 Tong, AW, Zhang, YA, Nemunaitis, J. Small interfering RNA for experimental cancer therapy. Curr Opin Mol Ther 2005;7:114–24Google ScholarPubMed
4 Bohula, EA, Salisbury, AJ, Sohail, M, Playford, MP, Riedemann, J, Southern, EM et al. The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Biol Chem 2003;278:15991–7CrossRefGoogle Scholar
5 Xiangbai, Wu, Yongzhi, Deng, Guobin, Wang, Kaixiong, Tao. Combining siRNAs at two different sites in the EGFR to suppress its expression, induce apoptosis, and enhance 5-fluorouracil sensitivity of colon cancer cells. J Surg Res 2006;27:1–8Google Scholar
6 Tuschl, T. Expanding small RNA interference. Nat Biotechnol 2002;20:446–8CrossRefGoogle ScholarPubMed
7 Zhang, M, Zhang, X, Bai, CX, Song, XR, Chen, J, Gao, L et al. Silencing the epidermal growth factor receptor gene with RNAi may be developed as a potential therapy for non small cell lung cancer. Genet Vaccines Ther 2005;3:5CrossRefGoogle ScholarPubMed
8 Lee, YJ, Imsumran, A, Park, MY, Kwon, SY, Yoon, HI, Lee, JH et al. Adenovirus expressing shRNA to IGF-1R enhances the chemosensitivity of lung cancer cell lines by blocking IGF-1 pathway. Lung Cancer 2007;55(3):279–86CrossRefGoogle ScholarPubMed
9 Jackson, AL, Bartz, SR, Schelter, J, Kobayashi, SV, Burchard, J, Mao, M et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 2003;21:635–7CrossRefGoogle ScholarPubMed
10 Brummelkamp, TR, Bernards, R, Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002;296:550–3CrossRefGoogle ScholarPubMed
11 Oldak, M, Malejczyk, J. Signal transduction mechanisms induced by epidermal growth factor receptor (EGFR) and their role in apoptosis regulation [in Polish]. Postepy Hig Med Dosw 1999;53:315Google ScholarPubMed
12 Harari, 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;49:427CrossRefGoogle ScholarPubMed
13 Shawver, LK, Slamon, D, Ullrich, A. Smart drugs: tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002;1:117CrossRefGoogle ScholarPubMed