Propofol‐induced miR‐219‐5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3‐mediated Wnt/β‐catenin signalling activation

Abstract

Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR‐219‐5p. Silencing of propofol‐induced miR‐219‐5p using anti‐miR‐219‐5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial‐mesenchymal transition of Huh7 and SMMC7721 cells via miR‐219‐5p induction. The molecular mechanism behind these findings is that propofol‐induced miR‐219‐5p inhibits HCC cell progression by targeting glypican‐3 and subsequently results in the inhibition of Wnt/β‐catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.

Monitoring of tumor growth and vascularization with repetitive ultrasonography in the chicken chorioallantoic-membrane-assay

“…3 Median Costs for a male, six weeks old Crt:NU(NCr)-Foxn1nu/nu mouse according to the 3 available distributers for nude mice in the specific region (Janvier Labs, Paris, France; Charles River Wiga GmbH, Sulzfeld, Germany; Envigo RMS GmbH, Roßdorf, Germany). 4 Gong et al 39 , Huang et al 40 , Robertson et al 41 , Xu et al 42 and Zhang et al 43 . 5 Resembled by the average running costs for SCID mice in our specific institution (Translational Animal Research Center, Gutenberg University Mainz).…”

GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3β axis

“…Accumulating evidence has indicated that propofol exerts a number of non-anaesthetic effects, including antitumour activity [5]. Recently, propofol was reported to trigger apoptosis and suppress proliferation, motility and invasion in multiple human cancers, including breast cancer, pancreatic cancer, ovarian cancer, gastric cancer, lung cancer and hepatocellular carcinoma [6][7][8][9][10]. However, the effect of propofol on OSCC cells remains unknown.…”

Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression

“…Indeed, many researchers proposed GPC3 as the target of effective cytotoxic agents against HCC [ 25 , 26 , 43 ]. Epigallocatechin-3-gallate, a polyphenol of the natural product green tea, in addition to sodium ascorbate, a form of vitamin C, was recently reported to exert their antiproliferative action against HCC through a marked reduction in GPC3 protein expression [ 25 , 33 ].…”