Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway.
Drug Dev Res
; 81(5): 544-550, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32096264
ABSTRACT
OBJECTIVE:
To study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells.METHODS:
The expression of TRIM14 in 5-fluorouracil (5-FU)- and oxaliplation (L-OHP)-resistant GC tissues and cells were determined by qRT-PCR and western blotting. PcDNA3.1-TRIM14 and shRNA-TRIM14 vector were transfected to 5-FU-resistant GC cells (SGC7901/5-FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5-FU-resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1-MK-3903 plasmid was transfected to SGC7901/5-FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting.RESULTS:
TRIM14 was significantly upregulated in 5-FU- and L-OHP-resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5-FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5-FU-resistant GC mice. The overexpression of MK-3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5-FU cells.CONCLUSION:
TRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Resistencia a Medicamentos Antineoplásicos
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Quinases Ativadas por AMP
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Serina-Treonina Quinases TOR
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Proteínas com Motivo Tripartido
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article