[en] Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of
melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved
challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine/thre onine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines in vitro
and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple
melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration,
and survival in all examined cell lines, with viability IC50 doses in the range of 0.18–2.6 μM.
Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and
STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma cell lines. Further in
vivo studies should be performed to determine the treatment potential of CCT196969 in
patients with treatment-naïve and resistant melanoma brain metastasis.
Disciplines :
Biochimie, biophysique & biologie moléculaire
Auteur, co-auteur :
Reigstad, Agathe; University of Bergen - UiB > Department of Biomedicine
Herdlevær, Christina Frantzen; University of Bergen - UiB > Department of Biomedicine
Rigg, Emma; University of Bergen - UiB > Department of Biomedicine
Hoang, Tuyen; University of Bergen - UiB > Department of Biomedicine
Bjørnstad, Ole Vidhammer; University of Bergen - UiB > Department of Biomedicine
Aasen, Synnøve Nymark; University og Bergen - UiB > Department of Biomedicine ; Western Norway University of Applied Sciences > Faculty of Health and Social Sciences
PREIS, Jasmin Renate ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
HAAN, Claude ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Sundstrøm, Terje; HaukelHaukeland University Hospital > Department of Neurosurgery ; University of Bergen - UiB > Department of Clinical Medicine
Thorsen, Frits; University of Bergen - UiB > Department of Biomedicine ; University of Bergen - UiB > Department of Biomedicine > Molecular Imaging Center
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells
Date de publication/diffusion :
09 septembre 2022
Titre du périodique :
PLoS ONE
eISSN :
1932-6203
Maison d'édition :
Public Library of Science, San Franscisco, Etats-Unis - Californie
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