%0 Journal Article
%T Systemic network analysis identifies XIAP and I¦ÊB¦Á as potential drug targets in TRAIL resistant BRAF mutated melanoma
%A Anna Zinoveva
%A Dagmar Kulms
%A Greta Del Mistro
%A Ines M¨¹ller
%A Martin Siegemund
%A Meike Hutt
%A Philippe Lucarelli
%A Roland E. Kontermann
%A Stefan Beissert
%A S¨¦bastien De Landtsheer
%A Thomas Sauter
%J Archive of "NPJ Systems Biology and Applications".
%D 2018
%R 10.1038/s41540-018-0075-y
%X IZI1551 is superior in killing melanoma cells than TRAIL or specific MAP kinase inhibitors. a Clonogenic outgrowth of mutBRAF A375 and Malme3M melanoma cells treated with dabrafenib (Dabra; 10£¿¦ÌM) for 8 days was compared to untreated cells (*p£¿¡Ü£¿0.05; ***p£¿¡Ü£¿0.001). b Parental and dabrafenib-conditioned melanoma cell lines A375 and Malme3M were treated with dabrafenib (Dabra; 10£¿¦ÌM) alone or in combination with trametinib (Trame; 1£¿¦ÌM). After 48£¿h apoptosis was determined using a Cell Death Detection ELISA (CDDE) (*p£¿¡Ü£¿0.05; **p£¿¡Ü£¿0.01; ***p£¿¡Ü£¿0.001; n.s.£¿=£¿not significant). c A375 melanoma cells were treated with increasing doses of izTRAIL or IZI1551 as indicated (ng/ml). After 24£¿h apoptosis was determined using a CDDE (*p£¿¡Ü£¿0.05; **p£¿¡Ü£¿0.01; ***p£¿¡Ü£¿0.001; n.s.£¿=£¿not significant). d The same dose kinetics of IZI1551 as in (c) was applied to primary human keratinocytes, fibroblasts and melanocytes. After 24£¿h apoptosis was determined using a CDDE (*p£¿¡Ü£¿0.05; ***p£¿¡Ü£¿0.001; n.s.£¿=£¿not significant). e Parental (par) and dabrafenib-conditioned (cond) melanoma cell lines A375 and Malme3M were treated with dabrafenib (Dabra; 10£¿¦ÌM) or IZI1551 (IZI; 50£¿ng/ml) alone or in combination. After 24£¿h of IZI1551 and 48£¿h of dabrafenib treatment apoptosis was determined using a CDDE (**p£¿¡Ü£¿0.01; ***p£¿¡Ü£¿0.001; n.s.£¿=£¿not significant) and f monitored by Western-blot analysis using antibodies against caspase-3 and PARP. ¦Á-tubulin served as loading control. For CDDE and clonogenic assay, the mean£¿¡À£¿SD of three independently performed experiments is shown. WBs represent one out of three independently performed experiment
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218484/