Characterization of two melanoma cell lines resistant to BRAF/MEK inhibitors (vemurafenib and cobimetinib).
Humans
Melanoma
/ pathology
Proto-Oncogene Proteins B-raf
/ genetics
Azetidines
/ pharmacology
Cell Line, Tumor
Drug Resistance, Neoplasm
/ drug effects
Protein Kinase Inhibitors
/ pharmacology
Piperidines
/ pharmacology
Vemurafenib
/ pharmacology
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Cell Survival
/ drug effects
BRAFi/MEKi
Cobimetinib
Drug resistance
Melanoma
Targeted therapy
Vemurafenib
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
22
02
2024
accepted:
12
08
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
BRAF (v-raf murine sarcoma viral oncogene homolog B1)/MEK (mitogen-activated protein kinase kinase) inhibitors are used for melanoma treatment. Unfortunately, patients treated with this combined therapy develop resistance to treatment quite quickly, but the mechanisms underlying this phenomenon are not yet fully understood. Here, we report and characterize two melanoma cell lines (WM9 and Hs294T) resistant to BRAF (vemurafenib) and MEK (cobimetinib) inhibitors. Cell viability was assessed via the XTT test. The level of selected proteins as well as activation of signaling pathways were evaluated using Western blotting. The expression of the chosen genes was assessed by RT-PCR. The distribution of cell cycle phases was analyzed by flow cytometry, and confocal microscopy was used to take photos of spheroids. The composition of cytokines secreted by cells was determined using a human cytokine array. The resistant cells had increased survival and activation of ERK kinase in the presence of BRAF/MEK inhibitors. The IC In summary, this work describes BRAF/MEK-inhibitor-resistant melanoma cells, allowing for better understanding the underlying mechanisms of resistance. The results may thus contribute to the development of new, more effective therapeutic strategies.
Sections du résumé
BACKGROUND
BACKGROUND
BRAF (v-raf murine sarcoma viral oncogene homolog B1)/MEK (mitogen-activated protein kinase kinase) inhibitors are used for melanoma treatment. Unfortunately, patients treated with this combined therapy develop resistance to treatment quite quickly, but the mechanisms underlying this phenomenon are not yet fully understood. Here, we report and characterize two melanoma cell lines (WM9 and Hs294T) resistant to BRAF (vemurafenib) and MEK (cobimetinib) inhibitors.
METHODS
METHODS
Cell viability was assessed via the XTT test. The level of selected proteins as well as activation of signaling pathways were evaluated using Western blotting. The expression of the chosen genes was assessed by RT-PCR. The distribution of cell cycle phases was analyzed by flow cytometry, and confocal microscopy was used to take photos of spheroids. The composition of cytokines secreted by cells was determined using a human cytokine array.
RESULTS
RESULTS
The resistant cells had increased survival and activation of ERK kinase in the presence of BRAF/MEK inhibitors. The IC
CONCLUSIONS
CONCLUSIONS
In summary, this work describes BRAF/MEK-inhibitor-resistant melanoma cells, allowing for better understanding the underlying mechanisms of resistance. The results may thus contribute to the development of new, more effective therapeutic strategies.
Identifiants
pubmed: 39175042
doi: 10.1186/s12964-024-01788-3
pii: 10.1186/s12964-024-01788-3
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Azetidines
0
cobimetinib
ER29L26N1X
Protein Kinase Inhibitors
0
Piperidines
0
Vemurafenib
207SMY3FQT
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
BRAF protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
410Subventions
Organisme : National Science Center, Poland
ID : SONATA, 2020/39/D/NZ5/02330
Informations de copyright
© 2024. The Author(s).
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