Article (Scientific journals)
CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells
Reigstad, Agathe; Herdlevær, Christina Frantzen; Rigg, Emma et al.
2022In PLoS ONE
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Abstract :
[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 :
Biochemistry, biophysics & molecular biology
Author, co-author :
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
External co-authors :
yes
Language :
English
Title :
CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells
Publication date :
09 September 2022
Journal title :
PLoS ONE
ISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 17 February 2023

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