Abstract
Glioblastoma is the most aggressive form of glioma, representing 15–20% of intracranial tumors and approximately half of gliomas in adults. Even though currently available combined therapy is used, the prognosis of patients with glioblastoma remains poor. In recent years, molecular targeted therapies have been developed when the molecular mechanism of glioblastomas is better understood. Epidermal growth factor receptor (EGFR) amplification/overexpression has been identified as the most common and important genetic aberration in glioblastomas, and it has become a prime target for molecular therapy of glioblastomas. In the present study, antisense EGFR RNA and EGFR siRNA were stably transfected into glioblastoma cells, resulting in significant suppression of EGFR expression, inhibition of cell viability and invasion, and induction of cell apoptosis both in vitro and in vivo. It seems that EGFR siRNA is more effective than antisense EGFR RNA. However, for obtaining high potency and favorable efficacy, the specific targeting site selection and screening are important when using either antisense EGFR RNA or EGFR siRNA treatment. It is expected that the delivery system with sufficiently high efficiency of transfection of antisense RNA and siRNA into tumor cells will be further developed. Combination of RNAi targeting multiple genes with conventional therapy will likely enhance the efficacy of glioblastoma treatment and will be a promising approach in the future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aigner A (2007) Nonviral in vivo delivery of therapeutic small interfering RNAs. Curr Opin Mol Ther 9:345–352
Arwert E, Hingtgen S, Figueiredo J-L, et al (2007) Visualizing the dynamics of EGFR activity and antiglioma therapies in vivo. Cancer Res 67:7335–7342
Batchelor TT, Betensky RA, Esposito JM, et al (2004) Age -dependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res 10:228–233
Behlke MA (2006) Progress towards in vivo use of siRNAs. Mol Ther 13:644–670
Benjamin R, Capparella J, Brown A (2003) Classification of glioblastoma multiforme in adults by molecular genetics. Cancer J 9:82–90
Biroccio A, Leonetti C, Zupi G (2003) The future of antisense therapy: combination with anticancer treatments. Oncogene 22:6579–6588
Boado RJ (2005) RNA interference and nonviral targeted gene therapy of experimental brain cancer. NeuroRx 2:139–150
Braasch DA, Jensen S, Liu Y, et al (2003) RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42:7967–7975
Chen SM, Wang Y, Xiao BK, et al (2008) Effects of blocking VEGF, hTERT and Bcl-xl by multiple shRNA expression vectors on the human laryngeal squamous carcinoma xenograft in nude mice. Cancer Biol Ther 7:734–739
Chi JT, Chang HY, Wang NN, et al (2003) Genome wide view of gene silencing by small interfering RNAs. Proc Natl Acad Sci USA 100:6343–6346
Decroe E, Silver PA (2002) Retrovirus-delivered siRNA. BMC Biotechnol 2:15
Dillin A (2003) The specifics of small interfering RNA specificity. Proc Natl Acad Sci USA 100:6289–6291
Dong L, Pu PY, Wang GX, et al (2006) Study on the alteration of EGFR and p53 in gliomas of Chinese patients. Chin J Pathol 35:232–236
Dong L, Pu P, Wang H, et al (2007) Cotransfection of antisense EGFR RNA and p53 gene effectively inhibits malignant glioma cell growth. Chin J Neurosurg 23:678–681
Downward J (2004) Use of RNA interference libraries to investigate oncogenic signaling in mammalian cells. Oncogene 23:8376–8383
Elbashir SM, Martinez J, Patkaniowska A, et al (2001) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate EMBO J 20:6877–6888
Engelhard HH (1998) Antisense oligonucleotide technology: potential use for the treatment of malignant brain tumors. Cancer Control 5:163–170
Fan QW, Weiss WA (2005) RNA interference against a glioma derived allele of EGFR induces blockade at G2/M. Oncogene 24:829–837
Far RK, Sczakiel G (2003) The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. Nucleic Acid Res 31:4417–4424
Frederick L, Wang XY, Eley G, et al (2000) Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 60:1383–1387
Furnari FB, Fenton T, Bachoo RM, et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683–2710
Grimm D, Kay M (2007) Combinatorial RNAi: a winning strategy for the race against evolving targets. Mol Ther 15:878–888
Halatsch ME, Schmidt U, Behnke-Mursch J, et al (2006) Epidermal growth factor receptor inhibition for the treatment of glioblastoma multiforme and other malignant brain tumours. Cancer Treat Rev 32:74–89
Hill JR, Kuriyama H, Isreal MA (1999) Molecular pathology of astrocytic brain tumors. Arch Neurol 56:439–441
Izquierdo M (2005) Short interfering RNAs as a tool for cancer gene therapy. Cancer Gene Ther 12:217–227
Jackson AL, Bartz SR, Schelter J, et al (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635–637
Jansen B, Zangemeister-Wittke U (2002) Antisense therapy for cancer-the time of truth. Lancet Oncol 3:672–683
Kang CS, Pu PY, Li YH, et al (2005) An in vitro study on the suppressive effect of glioma cell growth induced by plasmid-based small interference RNA (siRNA) targeting human epidermal growth factor receptor. J Neurooncol 74:267–273
Kim R, Tanabe K, Emi M, et al (2004) Potential roles of antisense therapy in the molecular targeting of genes involved in cancer. Int J Oncol 24:5–17
Kintage GJ, Templeton KL, Jenkins RB (2003) Recent advances in the molecular genetics of primary gliomas. Curr Opin Oncol 15:197–203
Kittler R, Buchholz F (2003) RNA interference: gene silencing in the fast lane. Semin Cancer Biol 13:259–265
Kondo Y, Hollingsworth EF, Kondo S (2004) Molecular targeting for malignant gliomas. Int J Oncol 24:1101–1109
Lal A, Glazer CA, Martinson HM, et al (2002) Mutant EGFR upregulates effectors of tumor invasion. Cancer Res 63:3335–3339
Laskin JJ, Sandler AB (2004) Epidermal growth factor receptor: a promising target in solid tumors. Cancer Treat Rev 30:1–17
Leirdal M, Sioud M (2002) Gene silencing in mammalian cells by performed small RNA duplexes. Biochem Biophys Res Commun 295:744–748
Li SD, Chen YC, Hackett MJ, et al (2008) Tumor targeted delivery of siRNA by self assembled nanoparticles. Mol Ther 16:163–169
Liu XW, Pu PY, Gao ZX (1998) Study on the gene expression of EGFR in human gliomas. Chin J Neurosurg 14:68–70
Liu KJ, Chen CT, Hu WS, et al (2004) Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenecity of EGFR-overexpressed human glioblastoma multiforme. Int J Oncol 24:581–590
Liu F, Conwell CC, Yuan X, et al (2007) Novel nonviral vectors target cellular signaling pathways regulated gene expression and reduced toxicity. J Pharmacol Exp Ther 321:777–783
Louis DN, Holland EC, Caircross JG (2001) Glioma classification, a molecular reappraisal. Am J Pathol 159:779–786
Ma Y, Chan CY, He ML (2007) RNA interference and antiviral therapy. World J Gastroenterol 13:5169–5179
Masiero M, Nardo G, Indraccolo S, et al (2007) RNA interference: implications for cancer treatment. Mol Aspects Med 28:143–166
Mason WP, Caircross JG (2008) Invited article: the expanding impact of molecular biology on the diagnosis and treatment of gliomas. Neurology 71:365–373
Miyagishi M, Hayashi M, Taira K (2003) Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells. Antisense Nucleic Acid Drug Dev 13:1–7
Mocellin S, Provenzano M (2004) RNA intereference: learning gene knock-down from cell physiology. J Transl Med 2:39
Moghal N, Sternberg PW (1999) Multiple positive and negative regulators of signaling by the EGF-receptor. Curr Opin Cell Biol 11:190–196
Muratovska A, Eccles MR (2004) Conjugate for efficiently delivery of short interfering RNA (siRNA) into mammalian cells. FEBS Lett 558:63–68
Nagy P, Arndt-Jovin DJ, Jovin TM (2003) Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor(erb1) and induce apoptosis in erb1-overexpressing cells. Exp Cell Res 285:39–49
Nishikawa R, Sugiyama T, Narita Y, et al (2004) Immunohistochemical analysis of the mutant epidermal growth factor, deltaEGFR, in glioblastoma. Brain Tumor Pathol 21:53–56
Nozaki M, Tada M, Kobayashi H, et al (1999) Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression. Neurooncol 1:124–137
Ohgaki H (2005) Genetic pathways to glioblastoma. Neuropathology 25:1–7
Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445–1453
Ohgaki H, Dessen P, Jourde B, et al (2004) Genetic pathways to glioblastoma: a population based study. Cancer Res 64:6892–6899
Okada Y, Hurwitz EE, Esposito JM, et al (2003) Selection pressure of Tp53 mutation and microenvironmental location influence EGFR gene amplification in human GBMs. Cancer Res 63:413–416
Pu P, Liu X, Liu A, et al (2000) Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo. J Neurosurg 92:132–139
Raizer JJ (2005) HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme. J Neurooncol 74:77–86
Robinson R (2004) RNAi therapeutics: how likely, how soon? PLoS Biol 2:18–20
Sache C, Echeverri CJ (2004) Oncology studies using siRNA libraries: the dawn of RNAi-based genomics. Oncogene 23:8384–8391
Sumimoto H, Kawakami Y (2007) Lentiviral vector mediated RNAi and its use for cancer research. Future Oncol 3:656–664
Tian XX, Lam PY, Hen J, et al (1998) Antisense epidermal growth factor receptor RNA transfection in human malignant glioma cells leads to inhibition of proliferation and induction of differentiation. Neuropathol Appl Neurobiol 24:389–396
Tian XX, Zhang YG, Du J, et al (2006) Effects of cotransfection of antisense EGFR and wild type PTEN cDNA on human glioblastoma cells. Neuropathology 26:178–187
Tomar RS, Matta H, Chaudhary PM (2003) Use of adeno-associated viral vector for delivery of small interfering RNA. Oncogene 22:5712–5715
Uprichard SL (2005) The therapeutic potential of RNA interference. FEBS Lett 579:5996–6007
Vickers TA, Koo S, Bennett F, et al (2003) Efficient reduction of target RNAs by small interfering RNA and RNase H dependent antisense agents. J Biol Chem 278:7108–7118
Yu JY, DeRuiter SL, Turner DL (2002) RNA interference by expression of short interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA 99:6047–6052
Zhang Y, Zhang YF, Bryant J, et al (2004) Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer. Clin Cancer Res 10:3667–3677
Acknowledgement
This work is supported by Tianjin Science and Technology Committee (Grant number 05YFJZJC1002 and 06YFSZSF01100), Program for New Century Excellent Talents in University, The Ministry of Education of the People's Republic of China (NCET-07–0615).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Pu, P., Kang, C., Jiang, H. (2009). Suppression of EGFR Expression by Antisense RNA and RNAi. In: Erdmann, V., Reifenberger, G., Barciszewski, J. (eds) Therapeutic Ribonucleic Acids in Brain Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_18
Download citation
DOI: https://doi.org/10.1007/978-3-642-00475-9_18
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-00474-2
Online ISBN: 978-3-642-00475-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)