MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway.
Biomed Pharmacother
; 106: 1419-1427, 2018 Oct.
Article
en En
| MEDLINE
| ID: mdl-30119215
ABSTRACT
OBJECTIVE:
In this study, we aimed to evaluate the expression and functions of MAPK8 in temozolomide (TMZ) -resistant glioblastoma cells as well as to explore the mechanism of TMZ resistance in glioblastoma cells.METHODS:
Gene Expression Omnibus (GEO) database was used for identifying the differentially expressed genes (DEGs) in TMZ resistant samples. The functional partner genes of TMZ were screened out by Gene-drug interaction network (STITCH) and the glioblastoma-related genes were selected by gene search engine with evidence sentences (Digsee). The interactions among identified DEGs and glioblastoma-related genes were detected by Search Tool for the Retrieval of Interacting Genes (STRING). The dysregulated pathways were identified by Gene set enrichment analysis (GSEA). qRT-PCR was performed to detect the expression level of MAPK8 in glioblastoma cells. Western blot was used to detect the expressions of MAPK8 and MAPK signaling pathway-related proteins. MTT assay was utilized to measure the cell viability of TMZ sensitive and resistant cells. Colony formation assay was performed to detect the clone ability and flow cytometry (FCM) assay was applied to identify the apoptosis rate of TMZ resistant glioblastoma cells.RESULTS:
MAPK8 was one of the DEGs and was up-regulated in TMZ resistant glioblastoma cells. The MAPK signaling pathway was activated in TMZ resistant glioblastoma cells under the condition of over-expression of MAPK8. The inhibition of MAPK8 restrained the colony formation, inducing apoptosis of TMZ resistant glioblastoma cells and suppressed the MAPK signaling pathway.CONCLUSION:
MAPK8 promoted the resistance to TMZ, accelerated cell proliferation and inhibited the apoptosis of glioblastoma cells via activating MAPK signaling pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Apoptosis
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Glioblastoma
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Resistencia a Antineoplásicos
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Antineoplásicos Alquilantes
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Sistema de Señalización de MAP Quinasas
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Dacarbazina
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Proteína Quinasa 8 Activada por Mitógenos
Límite:
Humans
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2018
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA