Abstract
Antitumor efficacy of the combined suicide gene therapy and radiotherapy was studied on the model of CT26 murine colon adenocarcinoma. CMV-FCU1-IRES-mGM-CSF-pGL3 construct with PEG-PEI-TAT (FCU1–mGM/5-FC) block copolymer as a vector was used for intratumoral administration. Tumors were irradiated with a single 5 Gy dose. The efficacy was evaluated according to the grade of tumor growth inhibition (T/C) and lifespan of the animals. Pronounced antitumor activity of the combined use of FCU1–mGM/5-FC system with radiotherapy on the background of prolonged lifespan and the synergism of the applied methods was revealed.
Similar content being viewed by others
References
Sverdlov, E.D., Genetic surgery—a right strategy to attack cancer, Curr. Gene Ther., 2011, vol. 11, no. 6, pp. 501–531.
Ardiani, A., Johnson, A.J., Ruan, H., Sanchez-Bonilla, M., Serve, K., and Black, M.E., Enzymes to die for: exploiting nucleotide metabolizing enzymes for cancer gene therapy, Curr. Gene. Ther., 2012, vol. 12, no. 2, pp. 77–91.
Springer, C.J. and Niculescu-Duvaz, I., Gene-directed enzyme prodrug therapy (GDEPT): choice of prodrugs, Adv. Drug Deliv. Rev., 1996, vol. 22, pp. 351–364.
Alekseenko, I.V., Snezhkov, E.V., Chernov, I.P., Pleshkan, V.V., Potapov, V.K., Sass, A.V., Monastyrskaya, G.S., Kopantzev, E.P., Vinogradova, T.V., Khramtsov, Yu.V., Ulasov, A.V., Rosenkranz, A.A., Sobolev, A.S., Bezborodova, O.A., Plyutinskaya, A.D., Nemtsova, E.R., Yakubovskaya, R.I., and Sverdlov, E.D., Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer, J. Trans. Med., 2015, vol. 13, no. 1, pp. 78–89.
Finocchiaro, L.M., Fiszman, G.L., Karara, A.L., and Glikin, G.C., Suicide gene and cytokines combined nonviral gene therapy for spontaneous canine melanoma, Cancer Gene Ther., 2008, vol. 15, no. 3, pp. 165–172.
Erbs, P., Regulier, E., Kintz, J., Leroy, P., Poitevin, Y., Exinger, F., Jund, R., and Mehtali, M., In vivo cancer gene therapy by adenovirus-mediated transfer of a bifunctional yeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene, Cancer Res., 2000, vol. 60, no. 14, pp. 3813–3822.
Tumor Models in Cancer Research, Second Edition Cancer Drug Discovery and Development, Teicher, B.A., Ed., Totowa, NY: Humana, 2010.
Clarke, R., Issues in experimental design and endpoint analysis in the study of experimental cytotoxic agents in vivo in breast cancer and other models, Breast Cancer Res. Treat., 1997, vol. 46, pp. 255–278.
Freytag, S.O., Barton, K.N., Brown, S.L., Narra, V., Zhang, Y., Tyson, D., Nall, C., Lu, M., Ajlouni, M., Movsas, B., and Ho Kim, J., Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancer, Mol. Ther., 2007, vol. 15, no. 9, pp. 1600–1606.
Donna, S., Shewach, D.S. and Lawrence, T.S., Antimetabolite radiosensitizers, J. Clin. Oncol., 2007, vol. 25, no. 26, pp. 4043–4050.
Rich, T.A., Shepard, R.C., and Mosley, S.T., Four decades of continuing innovation with fluorouracil: current and future approaches to fluorouracil chemoradiation therapy, J. Clin. Oncol., 2004, vol. 22, pp. 2214–2232.
Spalding, A.C. and Lawrence, T.S., New and emerging radiosensitizers and radioprotectors, Cancer Invest., 2006, vol. 24, pp. 444–456.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.A. Bezborodova, E.R. Nemtsova, A.R. Gevorkov, A.V. Boyko, J.B. Venediktova, I.V. Alekseenko, M.B. Kostina, G.S. Monastyrskaya, E.D. Sverdlov, E.V. Khmelevskiy, R.I. Yakubovskaya, 2016, published in Doklady Akademii Nauk, 2016, Vol. 470, No. 4, pp. 471–474.
Rights and permissions
About this article
Cite this article
Bezborodova, O.A., Nemtsova, E.R., Gevorkov, A.R. et al. Antitumor efficacy of combined gene and radiotherapy in animals. Dokl Biochem Biophys 470, 345–348 (2016). https://doi.org/10.1134/S1607672916050112
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1607672916050112