MODELING OF A SUBCUTANEOUS XENOGRATF OF HUMAN MELANOMA SKIN MEL RAC WITH NRAS MUTATION ON IMMUNODEFICIENT MICE FOR PRECLINICAL STUDYING THE TARGETING ANTICANCER DRUGS

Background. Development of new models of a human disseminative melanoma of skin with existence of a molecular and genetic target for specific therapy increases productivity of the preclinical researches in vitro and in vivo new the anti-melanoma drugs or their combinations. Such opportunity is realized by adaptation to in vivo of the original human pigment-free skin melanoma cell line mel Rac and receiving s. c. xenograft under monitoring, transplant, morphological, molecular and genetic (NRAS mutation) and chemotherapeutic (sensitivity to an inhibitor of NRAS a trametinib) characteristics. Objective. Receiving from the cell line mel Rac s. c. xenograft of a human pigmented melanoma of skin with a mutation of NRAS and sensitive to specific target therapy. Materials and methods. Human pigment-free skin melanoma cell line mel Rac from the Collection of Russian Cancer Research Center and immunodeficient female of Balb/c nude mice cultivation of Russian Cancer Research Center was used. Required characteristics are defined at a multiple s. c. transplanting in vivo by methods of transplant biology, a light microscopy, molecular genetics and the experimental chemotherapy. Sensitivity to a NRAS inhibitor to a trametinib was estimated under monitoring of rate of the tumor growth (V_t/V₀) on indexes, adequate for patients: existence of the complete remission and possibility of recurrence. Results. At s. c. transplantation of 10⁷ cell of mel Rac line are received cytological identical intertwined s. c. xenografts with a stable kinetics of growth on 4-9 passages (a latent phase 8 days, exponential - to 14 days, stationary - to 24 days) and existence of a mutation of NRAS. Trametinib in a single dose of 0,3 mg/kg caused the complete remission during a 14-day course and within 7 days after its cancellation without recurrence. Conclusion. Receiving with cell line mel Rac s. c. xenograft of a human pigment-free melanoma of skin with a mutation of NRAS and sensitive to specific target therapy is suitable for preclinical studying of the specific for this target new anti-melanoma drugs.

беспигментная меланома кожи человека, NRAS мутация, подкожный ксенографт, иммунодефицитные мыши, human pigment-free melanoma skin, NRAS mutation, subcutaneous xenograft, immunodeficient mice

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