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The influence of oligoribonucleotide complexes with D-mannitol on tumor formation in a murine model of B16 melanoma
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1  Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine

Published: 30 October 2019 by MDPI in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Malignant melanoma is considered to be one of the most aggressive forms of skin cancer - about 80% of skin cancer deaths are associated with this disease. Because melanoma is an immunogenic tumor, effective treatment is based on strategies to enhance the body's immune response. Recent studies have shown that oligoribonucleotides-D-mannitol (ORNs-D-M) complexes possess exhibit in particular antiviral, anti-inflammatory and immunomodulatory actions due to the activation of immune responses. Given the wide range of biological effects, we aimed to investigate the effect of ORNs-D-M on the development of B16 melanoma in mice by controlling tumor growth and genetic analysis of marker genes.

Methods. Adult female mice of a C57BL/6J line were used. Suspension of B16 mouse melanoma cell was subcutaneously introduced into the right posterior paw. For the experimental groups, the ORNs-D-M solution (in PBS) was injected once at concentrations of 1.4; 0.7; 0.35; 0.175 mg on animal. The control group received 100 μl of PBS. Tumor size was monitored during the experiment. Expression of T-cell markers (CD3, CD4, CD8, CD247), macrophage markers (CD68, CD163, NOS2), immunotherapy target genes (PDCD1, CD274, CTLA4, CTLA4 / del) and cytokine (IFNB1) were evaluated by real-time qPCR assay in peripheral blood of mice.

Results. Our investigations show that different concentrations of ORNs-D-M have the opposite effect on the growth of melanoma B16 tumors. In the group where animals received 1.4 mg of ORNs-D-M, the formation of the solid tumors was not observed; however, in the group with 0.7 mg dose, the average tumor volume was 97% lower than the non-drug group. In the case of lower concentrations, the average tumor size was 2-3 times higher than in the non-drug group. Also, we observed the changes in the expression of major marker genes. The mRNA expression levels of markers of T-cell counts CD3, CD4, CD8, and CD247, in groups with high concentrations of ORNs-D-M approached those of healthy animals. However, in mice, bearing melanoma recorded a decrease in mRNA levels of these genes. As well ORNs-D-M increases in the immune response to cancer and generally decreases the level of immunosuppression, which reflect in the increased expression of CD274, PDCD1, and IFNB1.

Keywords: B16 melanoma; ORNs-D-M; immune response to cancer