Sevoflurane inhibits the proliferation and invasion of hepatocellular carcinoma cells through regulating the PTEN/Akt/GSK3ß/ßcatenin signaling pathway by downregulating miR253p.
Int J Mol Med
; 46(1): 97-106, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32319540
ABSTRACT
Sevoflurane (Sevo) is one of the most frequently used volatile anesthetic agents in surgical oncology and has various effects on tumors, including inhibiting tumor growth, recurrence, and metastases; however, the molecular mechanisms are unknown. This study tried to investigate the influence of Sevo on hepatocellular carcinoma (HCC) cells and its possible mechanisms of action. The present study found that Sevo suppressed both the proliferative and invasive capabilities of both HCCLM3 and Huh7 cells in a dosedependent manner. Moreover, 53 differentially expressed microRNAs (miRNAs/miRs) in HCC cells that resulted from Sevo were screened out using miRNA microarray assay. In particular, miR253p displayed a significant decrease in response to Sevo treatment. Further studies showed that Sevo's inhibitory actions on HCC cells were attenuated by overexpression of miR253p but enhanced by its inhibitor. Phosphatidylinositol 3,4,5trisphosphate 3phosphatase and dualspecificity protein phosphatase PTEN (PTEN), a tumor suppressor gene, was directly targeted by miR253p and its expression was upregulated by Sevo. In addition, Sevo suppressed the expression of phosphorylatedprotein kinase B (pAkt) (S473), glycogen synthase kinase (GSK) 3ß (pGSK3ß) (S9), ßcatenin, cMyc and matrix metalloproteinase 9; whereas these inhibitory effects were reversed by miR253p overexpression. More importantly, Sevo's tumorsuppressive effects were enhanced by LY294002 (a PI3kinase inhibitor) but weakened by insulin growth factor1 (an agonist of the Akt signaling pathway). These data suggest that Sevo's antitumor effects on HCC could be explained, in part, by Sevo inhibiting the miR253p/PTEN/Akt/GSK3ß/ßcatenin signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Proteínas Proto-Oncogênicas c-akt
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Glicogênio Sintase Quinase 3 beta
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Sevoflurano
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article