| Abstract [eng] |
The aim of this dissertation was to determine the role of the expression of E3 ubiquitin ligases FBXW7 and MDM2, and their substrates p53and c–Myc in the development of metastatic melanoma and to evaluate possible new molecular targets for the treatment of this disease. The research was conducted at the National Cancer Institute, at the Life Sciences Center of Vilnius University and at the State Pathology Center of Vilnius University Hospital Santara Clinics. The human metastatic melanoma cell lines SK–ME –26, FM–94, FM–3 and the postoperative material from 100 patients who were diagnosed with dysplastic moles or melanoma that were surgically removed, were used in the study. The results of the study showed that oridonin, the activator of E3 ubiquitin ligase FBXW7, affects the cell viability of human metastatic melanoma cells by inhibiting the cell cycle and activating apoptosis. In the postoperative material of melanoma patients, an association was found between the low expression of E3 ubiquitin ligase FBXW7 and the depth of melanoma invasion and morphological type. The results confirmed the potential of the FBXW7 protein as a molecular target for anticancer therapy, and oridonin as an activator of FBXW7 could be a potential therapeutic tool for the treatment of melanoma. The results of the study are useful for scientists and clinicians studying the molecular mechanisms in the development of melanoma and possible molecular targets for the treatment of melanoma. The results obtained could help model individualized treatment for melanoma. |
