Abstract
High expression of multidrug resistance-associated protein 1 (MRP1) in tumor cells reduces effectiveness of chemotherapy drugs. In this study, we screened MRP1 interfering RNA (MRP1-siRNA) molecules that are able to reverse etoposide (VP16) resistance in multidrug resistance rat glioma cell line C6/VP16, and identified one siRNA molecule that is able to effectively deplete the expression of MRP1 gene and reverse tumor cells resistance to etoposide. Since siRNA instability limits its application in treatment of diseases, we next tested silencing effect of chitosan-MRP1-siRNA nanoparticles and found that the nanoparticles with N:P ratio 175 are able to effectively inhibit MRP1 mRNA and protein expression. Our data demonstrate that chitosan can be used as siRNA carrier for high efficient gene silencing in tumor cells.
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Mellor, H. R., Callaghan, R., et al. (2008). Resistance to chemotherapy in cancer: A complex and integrated cellular response. Pharmacology, 81(4), 275–300.
Baguley, B. C. (2010). Multiple drug resistance mechanisms in cancer. Molecular Biotechnology, 46(3), 308–316.
de Faria, G. P., de Oliveira, J. A., de Oliveira, J. G., et al. (2008). Differences in the expression pattern of P-glycoprotein and MRP1 in low-grade and high-grade gliomas. Cancer Investigation, 26(9), 883–889.
Li, Q. F., Xu, H. T., Wang, L., et al. (2012). Establishment of multidrug resistant glioma cell line C6/VP16. Chinese Journal of Clinical Neurosurgery, 7(07), 414–416.
Loe, D. W., Deeley, R. G., Cole, S. P., et al. (1996). Biology of the multidrug resistance-associated protein, MRP. European Journal of Cancer, 32A(6), 945–957.
O’Connor, R., O’Leary, M., Ballot, J., et al. (2007). A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer. Cancer Chemotherapy and Pharmacology, 59(1), 79–87.
Shabalina, S. A., Spiridonov, A. N., et al. (2006). Computational models with thermodynamic and composition features improve siRNA design. BMC Bioinformatics, 7, 65.
Holen, T., Amarzguioui, M., et al. (2002). Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucleic Acids Research, 30(8), 1757–1766.
Kars, M. D., Iseri, O. D., et al. (2010). Drug resistant breast cancer cells overexpress ETS1 gene. Biomedicine & Pharmacotherapy, 64(7), 458–462.
Ma, J. Y., Huang, S. L., He, W., et al. (2005). Study of effects of intracranial injection of chitosan on serum levels of NSE and S-100 protein, and brain tissue in rats. Chinese Journal of Clinical Neurosurgery, 10(2), 127–128.
Katas, H., & Alpar, H. O. (2006). Development and characterisation of chitosan nanoparticles for siRNA delivery. Journal of Controlled Release, 115(2), 216–225.
Liu, X., Howard, K. A., et al. (2007). The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials, 28(6), 1280–1288.
Mao, H. Q., Roy, K., et al. (2001). Chitosan-DNA nanoparticles as gene carriers: synthesis, characteriza tion and transfection efficiency. Journal of Controlled Release, 70(3), 399–421.
Panyam, J., Labhasetwar, V., et al. (2003). Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews, 55(3), 329–347.
Douglas, K. L., Tabrizian, M., et al. (2005). Effect of experimental parameters on the formation of alginate-chitosan nanoparticles and evaluation of their potential application as DNA carrier. Journal of Biomaterials Science, Polymer Edition, 16(1), 43–56.
Csaba, N., Koping-Hoggard, M., et al. (2009). Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. International Journal of Pharmaceutics, 382(1–2), 205–214.
Koping-Hoggard, M., Tubulekas, I., et al. (2001). Chitosan as a nonviral gene delivery system. Structure-property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo. Gene Therapy, 8(14), 1108–1121.
MacLaughlin, F. C., Mumper, R. J., Wang, J., et al. (1998). Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery. Journal of Controlled Release, 56(1–3), 259–272.
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Xu, H., Nie, X., Wu, L. et al. Down-Regulation of MRP1 Expression in C6/VP16 Cells by Chitosan-MRP1-siRNA Nanoparticles. Cell Biochem Biophys 72, 227–233 (2015). https://doi.org/10.1007/s12013-014-0442-2
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DOI: https://doi.org/10.1007/s12013-014-0442-2