IMIBIO-SL   20937
INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES BIOLOGICAS DE SAN LUIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
VEMURAFENIB REVERTS HYPOXIA-INDUCED INCREASE IN CELL VIABILITY OF BRAFV600E MELANOMA CELLS
Autor/es:
MELINA CASTRO; YAMILA RODRIGUEZ; LUDMILA CAMPOS; SERGIO E ALVAREZ; CELIA PEREZ; DARÍO RAMIREZ
Lugar:
Mar del Plata
Reunión:
Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016
Resumen:
Melanoma is the most aggressive form of skin cancer with a high mortality percentage. Half of melanoma patients display the BRAFV600E kinase mutation. Indeed, Food and Drug administration FDA and ANMAT have approved the use of vemurafenib and dabrafenib (BRAF inhibitors) in melanoma patients. Unfortunately, patients develop resistance after a short period of disease control, indicating that new targets are needed. In that regard, several evidences confirm that tumor microenvironment modulate proliferation, migration and acquired resistance of cancer. recisely, hypoxia is a remarable feature of this picture that control cancer growth and progression. Thus, the aim of this study as to elucidate how hypoxia influences the viability of melanoma cells. eused to melanoma cell lines Skmel2 (BRAF WT) and Lu1205 (BRAF V600E). Surprisingly, hypoxia exerts a differential effect according to the culture conditions hile decreases viability of melanoma cells cultured in the presence of fetal bovine serum FBS, it partially protects of the reduced viability observed under serum deprivation conditions. To further investigate the effect in absence of serum, e used pharmacological inhibitors of different signaling pathays. Certainly, inhibition of F, , E and hypoxia inducible factor alpha HFa pathays do not have an effect on viability of Skmel2 melanoma cells in hypoxia. In the other hand, HFa is crucial for the hypoxiainduced protection of Lu1205 melanoma cell viability. Interestingly, inhibition of BRAF with vemurafenib also reverts the effect of hypoxia in Lu1205 melanoma cells. Altogether, these results suggest that viability of cancer cells in the hypoxic zones of the tumor is not reduced by the deficiency of growth factors, but may be diminished by inhibition of BRAF with vemurafenib.