Targeting SIRT2 Sensitizes Melanoma Cells to Cisplatin via an EGFR-Dependent Mechanism.
Cell Line, Tumor
Cisplatin
/ adverse effects
Drug Resistance, Neoplasm
/ genetics
ErbB Receptors
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Histones
/ genetics
Humans
MAP Kinase Signaling System
/ drug effects
Melanoma
/ drug therapy
Proto-Oncogene Proteins c-akt
Sirtuin 2
/ antagonists & inhibitors
raf Kinases
/ genetics
EGFR
SIRT2
cisplatin
melanoma
resistance
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
10 May 2021
10 May 2021
Historique:
received:
29
03
2021
revised:
27
04
2021
accepted:
05
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
Melanoma cells are resistant to most anticancer chemotherapeutics. Despite poor response rates and short-term efficacy, chemotherapy remains the main approach to treating this cancer. The underlying mechanisms of the intrinsic chemoresistance of melanoma remain unclear, but elucidating these mechanisms is important to improve the efficacy of chemotherapy regimens. Increasing evidence suggests that sirtuin 2 (SIRT2) plays a key role in the response of melanoma cells to chemotherapeutics; thus, in the present study, we evaluated the impact of shRNA-mediated and pharmacological inhibition of SIRT2 on the sensitivity of melanoma cells to cisplatin, which is used in several regimens to treat melanoma patients. We found that cells with SIRT2 inhibition revealed increased sensitivity to cisplatin and exhibited increased accumulation of γ-H2AX and reduced EGFR-AKT-RAF-ERK1/2 (epidermal growth factor receptor-protein B kinase-RAF kinase-extracellular signal-regulated kinase 1/2) pathway signaling compared to control cells. Thus, our results show that sirtuin 2 inhibition increased the in vitro efficacy of cisplatin against melanoma cells.
Identifiants
pubmed: 34068624
pii: ijms22095034
doi: 10.3390/ijms22095034
pmc: PMC8126047
pii:
doi:
Substances chimiques
H2AX protein, human
0
Histones
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
raf Kinases
EC 2.7.11.1
SIRT2 protein, human
EC 3.5.1.-
Sirtuin 2
EC 3.5.1.-
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Centre
ID : 2015/17/B/NZ5/00142
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