High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

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dc.contributor.authorZajakina, Anna
dc.contributor.authorVasilevska, Jelena
dc.contributor.authorZhulenkovs, Dmitry
dc.contributor.authorSkrastina, Dace
dc.contributor.authorSpaks, Artjoms
dc.contributor.authorPlotniece, Aiva
dc.contributor.authorKozlovska, Tatjana
dc.date.accessioned2021-06-18T10:10:01Z
dc.date.available2021-06-18T10:10:01Z
dc.date.issued2014-06-20
dc.descriptionCopyright: Copyright 2014 Elsevier B.V., All rights reserved.
dc.description.abstractBackground: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.en
dc.description.statusPeer reviewed
dc.format.extent16
dc.format.extent7687025
dc.identifier.citationZajakina, A, Vasilevska, J, Zhulenkovs, D, Skrastina, D, Spaks, A, Plotniece, A & Kozlovska, T 2014, 'High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model', BMC Cancer, vol. 14, no. 1, 460. https://doi.org/10.1186/1471-2407-14-460
dc.identifier.doi10.1186/1471-2407-14-460
dc.identifier.issn1471-2407
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/5213
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84902714392&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofBMC Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject4 T1 tumor
dc.subject5-fluorouracil
dc.subjectCombined cancer treatment
dc.subjectCytotoxic effect
dc.subjectSemliki Forest virus
dc.subject3.2 Clinical medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectGenetics
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleHigh efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor modelen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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