MORPHINE MODULATES NF-kB ACTIVATION AND MOTILITY OF MELANOMA CELLS

SANCHEZ ES; CAMPOS L; CASTRO M; RODRIGUEZ Y; ALVAREZ SE

Mendoza

Congreso; XXXI Reunión Anual de la Sociedad de Biología de Cuyo; 2013

Melanoma is the most aggressive type of skin cancer and its progression involves invasion of tumor cells to distant tissues. Melanoma is resistant to chemotherapy and usually, morphine treatment constitutes the only way to alleviate the pain associated to the later stages of the disease. Since activation of NF-kB is a hallmark of many cancers, we decided to examine the role of morphine in this pathway and its contribution to the migration of melanoma cells. Preliminary studies were performed in murine B16 cells and indicate that morphine decrease both IKK activation and cell migration as assessed in a Boyden Chamber. Because most of the melanoma patients display the mutation BRAFV600E, we also used two human cells lines which differ in the status of the BRAF protein: SKMel2 (BRAF wild type) and Lu1205 (mutant BRAF). Remarkably, low (10 nM) and high (1 mM) doses of morphine stimulate IkB alpha degradation in SKMel 2 cells, while it has no effect on Lu1205 cells. On the other hand, by using the scratch (wound healing) assay, we show that morphine increases migration of Lu1205 cells, but diminish migration of SKMel2 cells. These results indicate that the effect of morphine in melanoma is cell type dependent. On the other hand, they reinforce the concept that morphine treatment and doses should be handled with care because of the possible consequences to the progression of the later stages of the disease.