Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30–70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Jauchem JR (2008) Effects of low-level radio-frequency (3 kHz–300 GHz) energy on human cardiovascular, reproductive, immune, and other systems: a review of the recent literature. Int J Hyg Environ Health 211:1–29
Hardell L, Sage C (2008) Biological effects from electromagnetic field exposure and public exposure standards. Biomed Pharmacother 62:104–109
Yoon SY, Kim KT, Jo SJ, Cho AR, Jeon SI, Choi HD, Kim KH, Park GS, Pack JK, Kwon OS, Park WY (2011) Induction of hair growth by insulin-like growth factor-1 in 1763 MHz radiofrequency-irradiated hair follicle cells. PLoS ONE 6:e28474. doi:10.1371/journal.pone.0028474
Volpe P (2003) Interactions of zero-frequency and oscillating magnetic fields with biostructures and biosystems. Photochem Photobiol Sci 2:637–648
Ćosić I, Pirogova E, Vojisavljević V, Fang Q (2006) Electromagnetic properties of biomolecules. FME Trans 34:10
Montagnier L, Del Giudice E, Aissa J, Lavallee C, Motschwiller S, Capolupo A, Polcari A, Romano P, Tedeschi A, Vitiello G (2015) Transduction of DNA information through water and electromagnetic waves. Electromagn Biol Med 34:106–112. doi:10.3109/15368378.2015.1036072
Del Giudice E, Fleischmann M, Preparata G, Talpo G (2002) On the “unreasonable” effects of ELF magnetic fields upon a system of ions. Bioelectromagnetics 23:522–530. doi:10.1002/bem.10046
Butters JT, Figueroa XA, Butters BM (2014) Non-thermal radio frequency stimulation of tubulin polymerization in vitro: a potential therapy for cancer treatment. Open J Biophys 4:22
Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H, Nagano O (2016) The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-). Cancer Res 76:2954–2963. doi:10.1158/0008-5472
Cominelli M, Grisanti S, Mazzoleni S, Branca C, Buttolo L, Furlan D, Liserre B, Bonetti MF, Medicina D, Pellegrini V, Buglione M, Liserre R, Pellegatta S, Finocchiaro G, Dalerba P, Facchetti F, Pizzi M, Galli R, Poliani PL (2015) EGFR amplified and overexpressing glioblastomas and association with better response to adjuvant metronomic temozolomide. J Natl Cancer Inst. doi:10.1093/jnci/djv041
Klingler S, Guo B, Yao J, Yan H, Zhang L, Vaseva AV, Chen S, Canoll P, Horner JW, Wang YA, Paik JH, Ying H, Zheng H (2015) Development of resistance to EGFR-targeted therapy in malignant glioma can occur through EGFR-dependent and -independent mechanisms. Cancer Res 75:2109–2119. doi:10.1158/0008-5472
Schulte A, Liffers K, Kathagen A, Riethdorf S, Zapf S, Merlo A, Kolbe K, Westphal M, Lamszus K (2013) Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with upregulation of EGFRvIII and PI3Kp110delta. Neuro Oncol 15:1289–1301. doi:10.1093/neuonc/not093
Ramis G, Thomas-Moya E, Fernandez de Mattos S, Rodriguez J, Villalonga P (2012) EGFR inhibition in glioma cells modulates Rho signaling to inhibit cell motility and invasion and cooperates with temozolomide to reduce cell growth. PLoS ONE 7:e38770. doi:10.1371/journal.pone.0038770
Hirono S, Umeyama H, Moriguchi I (1984) Electrostatic potential images of drugs targetting dopamine receptors. Chemical Pharm Bull 32:3061–3065
Grant BJ, Gheorghe DM, Zheng W, Alonso M, Huber G, Dlugosz M, McCammon JA, Cross RA (2011) Electrostatically biased binding of kinesin to microtubules. PLoS Biol 9:e1001207 doi:10.1371/journal.pbio.1001207
Weiner PK, Langridge R, Blaney JM, Schaefer R, Kollman PA (1982) Electrostatic potential molecular surfaces. Proc Natl Acad Sci USA 79:3754–3758
Ozawa T, James CD (2010) Establishing intracranial brain tumor xenografts with subsequent analysis of tumor growth and response to therapy using bioluminescence imaging. J Vis Exp. doi:10.3791/1986
Pisano A, Santolla MF, De Francesco EM, De Marco P, Rigiracciolo DC, Perri MG, Vivacqua A, Abonante S, Cappello AR, Dolce V, Belfiore A, Maggiolini M, Lappano R (2016) GPER, IGF-IR, and EGFR transduction signaling are involved in stimulatory effects of zinc in breast cancer cells and cancer-associated fibroblasts. Mol Carcinog. doi:10.1002/mc.22518
Yu Y, Sun Y, He S, Yan C, Rui L, Li W, Liu Y (2012) Neuronal Cbl controls biosynthesis of insulin-like peptides in Drosophila melanogaster. Mol Cell Biol 32:3610–3623. doi:10.1128/MCB.00592-12
Flageng MH, Knappskog S, Haynes BP, Lonning PE, Mellgren G (2013) Inverse regulation of EGFR/HER1 and HER2-4 in normal and malignant human breast tissue. PLoS ONE 8:e74618. doi:10.1371/journal.pone.0074618
Li Y, Vongsangnak W, Chen L, Shen B (2014) Integrative analysis reveals disease-associated genes and biomarkersMammoth mountains for prostate cancer progression. BMC Med Genomics 7(Suppl 1):S3. doi:10.1186/1755-8794-7-S1-S3
Zhao Y, Xiao A, Dipierro CG, Abdel-Fattah R, Amos S, Redpath GT, Carpenter JE, Pieper RO, Hussaini IM (2008) H-Ras increases urokinase expression and cell invasion in genetically modified human astrocytes through Ras/Raf/MEK signaling pathway. Glia 56:917–924. doi:10.1002/glia.20667
Lo HW, Hung MC (2006) Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer 94:184–188
We thank all members of IVY Center for Advanced Brain Tumor Treatment at Swedish Neuroscience Institute for useful discussion of experimental approaches and data. This work was carried out through the general support of Center for Advanced Brain Tumor Treatment General Fund, Nativis Inc General Support grant and Swedish Foundation.
MB and JB developed Voyager technology and designed devices; IU, HF, JGY and PH designed experimental set up, performed cell culture experiments, and analyzed the data; IU, CC, XF, and HF wrote and corrected paper. MP, TN and TO designed, conducted, data analyzed in vivo experiments.
Conflict of interests
J.B. and M.B. are employed full time at Nativis, Inc. I.U. and X.F. are partially employed by Nativis, Inc. CC serves as a consultant for Nativis, Inc.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Ulasov, I.V., Foster, H., Butters, M. et al. Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy. J Neurooncol 133, 257–264 (2017). https://doi.org/10.1007/s11060-017-2440-x
- Electromagnetic energy
- Radio frequency