The full recovery of mice (Mus Musculus C57BL/6 strain) from virus–induced sarcoma after treatment with a complex of DDMC delivery system and sncRNAs

• Published in: Non-coding RNA research 2019-06, Vol.4 (2), p.69-78
• Main Authors: Klimenko, Oxana V., Sidorov, Alexey
• Format: Article
• Language: English
• Subjects: DDMC vector; Epigenetic therapy; Mice; Sarcoma; Small non-coding RNAs; Src tyrosine kinase
• ISSN: 2468-0540; 2468-0540
• DOI: 10.1016/j.ncrna.2019.03.001

Virus-induced cellular genetic modifications result in the development of many human cancers. In our experiments, we used the RVP3 cell line, which produce primary mouse virus-induced sarcoma in 100% of cases. Inbreed 4-week-old female C57BL/6 mice were injected subcutaneously in the interscapular region with RVP3 cells. Three groups of mice were used. For treatment, one and/or two intravenous injections of a complex of small non-coding RNAs (sncRNAs) a-miR-155, piR-30074, and miR-125b with a 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC) delivery system were used. The first group consisted of untreated animals (control). The second group was treated with one injection of complex DDMC/sncRNAs (1st group). The third group was treated with two injections of complex DDMC/sncRNAs (2nd group). The tumors were removed aseptically, freed of necrotic material, and used with spleen and lungs for subsequent RT-PCR and immunofluorescence experiments, or stained with Leishman-Romanowski dye. As a result, the mice fully recovered from virus-induced sarcoma after two treatments with a complex including the DDMC vector and a-miR-155, piR-30074, and miR-125b. In vitro studies showed genetic and morphological transformations of murine cancer cells after the injections. Treatment of virus-induced sarcoma of mice with a-miR-155, piR-30074, and miR-125b as active component of anti-cancer complex and DDMC vector as delivery system due to epigenetic-regulated transformation of cancer cells into cells with non-cancerous physiology and morphology and full recovery of disease. •Complex of a-miR-155, piR-30074, and miR-125b with DDMC vector induced full recovery from virus-induced sarcoma in mice.•Complex of DDMC/a-miR-155, piR-30074, and miR-125b transformed sarcoma cells into other types non-cancerous cells.•Tumor regression was connected with transformation of cancer cells.•Complex of the DDMC vector with a-miR-155, piR-30074, and miR-125b induced apoptosis in transformed cells.