Advanced-stage melanomas are highly aggressive and refractable to a variety of therapeutic regimens. Low effectiveness of chemotherapy is due to a progressive state of drug resistance. Cisplatin, which is the most effective single agent for the treatment of melanomas, improves the disease free interval of no more than 15% of the melanoma-bearing patients. Neuroectodermal tumors as melanomas are characterized by the accumulation of glycosyphingolipids and gangliosides, which are ceramide-derived molecules. Several studies indicate that the enzyme which converts ceramide into glycosphingolipids, the glucosylceramide-synthase, is usually upregulated in chemoresistant cells. The aim of this project is to evaluate whether the remodeling of glycosphingolipids leads to sensitivity towards cisplatin in a melanoma cell line. Cisplatin resistant cell lines will be generated through selection. These cell lines and the parental cell line will be then compared regarding the expression of a panel of proteins identified previously in a proteomic study; these cell lines will be either treated or not with inhibitors of glucosylceramide-synthase and further evaluated regarding sensitivity to cisplatin.
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