Sheng-Qun Liu1, Jing-Liang Zhang1, Zhan-Wen Li1, Zhen-Hua Hu1, Zhe Liu1, Yi Li2. 1. Department of Anesthesiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China. 2. Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China.
Abstract
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/β-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, β-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/β-catenin and PI3K/ AKT pathways via down-regulation of miR-374a. Besides, miR-374a affected propofol-treated HepG2 cells by targeting TP53.
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/β-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, β-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/β-catenin and PI3K/ AKT pathways via down-regulation of miR-374a. Besides, miR-374a affected propofol-treated HepG2 cells by targeting TP53.
Authors: Dongmei Wang; Na Xing; Tao Yang; Junqi Liu; Huaping Zhao; Juan He; Yanqiu Ai; Jianjun Yang Journal: Cancer Med Date: 2020-08-07 Impact factor: 4.452