Sevoflurane inhibits the proliferation and invasion of hepatocellular carcinoma cells through regulating the PTEN/Akt/GSK?3?/??catenin signaling pathway by downregulating miR?25?3p.

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 dose?dependent manner. Moreover, 53 differentially expressed microRNAs (miRNAs/miRs) in HCC cells that resulted from Sevo were screened out using miRNA microarray assay. In particular, miR?25?3p 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 miR?25?3p but enhanced by its inhibitor. Phosphatidylinositol 3,4,5?trisphosphate 3?phosphatase and dual?specificity protein phosphatase PTEN (PTEN), a tumor suppressor gene, was directly targeted by miR?25?3p and its expression was upregulated by Sevo. In addition, Sevo suppressed the expression of phosphorylated?protein kinase B (p?Akt) (S473), glycogen synthase kinase (GSK) 3? (p?GSK3?) (S9), ??catenin, c?Myc and matrix metalloproteinase 9; whereas these inhibitory effects were reversed by miR?25?3p overexpression. More importantly, Sevo's tumor?suppressive effects were enhanced by LY294002 (a PI3?kinase inhibitor) but weakened by insulin growth factor?1 (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 miR?25?3p/PTEN/Akt/GSK?3?/??catenin signaling pathway.

SUBMITTER: Cao Y 

PROVIDER: S-EPMC7255470 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature