4.2 Article

Propofol Inhibits Proliferation, Migration, Invasion and Promotes Apoptosis Through Down-Regulating miR-374a in Hepatocarcinoma Cell Lines

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CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 49, 期 6, 页码 2099-2110

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KARGER
DOI: 10.1159/000493814

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Hepatocellular carcinoma; Propofol; miR-374a; Wnt/beta-catenin; PI3K/AKT

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Background: Propofol is a commonly used anaesthetic with controversial effects on cancer cells. We aimed to explore the functional roles of propofol in hepatocellular carcinoma (HCC) cells as well as the underlying mechanisms. Methods: HepG2 and SMMC-7721 cells were used in this study. Firstly, the effects of propofol on cell viability, migration, invasion, apoptosis, and involved proteins were assessed by Cell Counting Kit-8 assay, Transwell assay, flow cytometry assay and Western blot analysis, respectively. Subsequently, alteration of miR-374a after stimulation of propofol was analyzed by qRT-PCR. miR-374a was overexpressed and the alteration of proteins in the Wnt/beta-catenin and PI3K/AKT pathways was detected by Western blot analysis. The downstream factor of miR-374a was finally studied. Results: Propofol inhibited cell viability, migration and invasion but promoted apoptosis of HepG2 and SMMC-7721 cells. Meanwhile, cyclinD1, matrix metalloproteinase (MMP)-2 and MMP-9 were down-regulated while Bax/Bcl-2, cleaved caspase-3 and cleaved caspase-9 were up-regulated by propofol. Then, miR-374a level was reduced by propofol. Expression of Wnt3a, beta-catenin, p-PI3K and p-AKT was decreased by propofol, whereas these decreases were reversed by miR-374a overexpression. Finally, TP53 was proven to be target of miR-374a in HepG2 cells. Conclusion: Propofol inhibited cell proliferation, migration and invasion while promoted cell apoptosis of HepG2 and SMMC-7721 cells through inhibiting the Wnt/beta-catenin and PI3K/AKT pathways via down-regulation of miR-374a. Besides, miR-374a affected propofol-treated HepG2 cells by targeting TP53. (C) 2018 The Author(s) Published by S. Karger AG, Basel

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