MODELING OF A SUBCUTANEOUS XENOGRAFT OF HUMAN SKIN MELANOMA MEL CHER WITH V600E BRAF MUTATION IN IMMUNODEFICIENT MICE FOR PRECLINICAL STUDY THE TARGETING ANTICANCER DRUGS

Abstract

Introduction. Development of new models of a human disseminated skin melanoma of the with molecular-genetic targets for specific therapy increases productivity of the preclinical researches new the anti-melanoma drugs or their combinations in vitro and in vivo. Such opportunity is realized by adaptation in vivo of the original human pigmented skin melanoma cell line mel Cher and receiving subcutaneous (s. c.) xenograft under monitoring of transplant, morphological, molecular-genetic (V600E BRAF mutation) and chemotherapeutic (sensitivity for the inhibitor of BRAF kinases to a vemurafenib) characteristics. Objective: receiving from the cell line mel Cher s. c. xenogratft of the human pigmented skin melanoma with V600E BRAF mutation and sensitive to specific target therapy. Materials and methods. Human pigmented skin melanoma cell line mel Cher from the Collection of Russian Cancer Research Center and immunodeficient Balb/c nude female mice cultivated in Russian Cancer Research Center was used. Required characteristics are defined by multiple s. c. transplanting in vivo by methods of transplant biology, a light microscopy, molecular-genetics and the experimental chemotherapy. Sensitivity to a BRAF kinase inhibitor to a vemurafenib was estimated under monitoring of the tumor growth rate (Vt/V0) on indexes, adequate for patients: existence of the complete remission and possibility of recurrence. Results. When s. c. transplantation of 107 cell of mel Cher line cytological identical intertwined s. c. xenografts with a stable growth kinetics on 4-9 passages (a latent phase 8 days, exponential - to 14 days, stationary - to 24 days) and existence of a mutation of V600E BRAF have been recieved. Vemurafenib in a single dose of 75 mg/kg caused the complete remission during a 15-day course and within 7 days after its cancellation - with the subsequent recurrence. Conclusion: receiving from the cell line mel Cher s. c. xenogratft of a human pigmented melanoma of skin with a mutation of V600E BRAF and sensitive to specific target therapy is suitable for preclinical studying of the new anti-melanoma drugs specific for this target.