Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis

Abstract

Propofol is a commonly used drug for sedation and general anesthesia during cancer surgery. Previous studies indicate that propofol exerts anti-tumor effect in various cancers. The aim of this study was to investigate the underlying molecular mechanism of propofol in liver cancer. The effects of propofol on liver cancer cells were evaluated by cell viability assay, colony formation assay, and tumor xenograft model. Dysregulated lncRNAs of propofol-treated liver cancer cells were evaluated by transcriptome RNA sequencing. The underlying molecular mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in propofol-induced anti-tumor effects were evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound scratch healing assay, transwell cell migration and invasion assay, TUNEL staining, fluorescence in situ hybridization, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). We found that propofol suppressed proliferation, migration, invasion, and tumor xenograft growth of liver cancer cells in a dose-dependent manner. Exosomes transfer from propofol-treated cells inhibited proliferation, migration, and invasion and promoted apoptosis of liver cancer cells. Transcriptional profiling of propofol-treated liver cancer cells identified CASC9 as significantly downregulated lncRNA in cells and exosomes. Enforced CASC9 expression partially rescued the inhibitory effects of propofol on liver cancer cells. Furthermore, CASC9 was found to interact directly with EZH2 and epigenetically regulated PTEN expression. Restoration of CASC9 partially abrogated the inhibition of propofol on Akt/mTOR signaling. Our results indicated that propofol exerted anti-tumor effects by downregulating CASC9, and subsequently suppressed Akt/mTOR signaling. Our findings provided a novel insight into propofol-induced anti-tumor effects in liver cancer.

Investigating the Influence of Anaesthesiology for Cancer Resection Surgery on Oncologic Outcomes: The Role of Experimental In Vivo Models

“…The xenograft model also requires quality control because many cell lines have unknown sources or poorly documented receptor expression, and regulatory safeguards are needed to protect researchers from the high communicability risk from handling human cancer tissue [ 16 , 18 ]. Despite these shortcomings, xenograft models have been used extensively to identify potential molecular mechanisms underlying the observed anti-tumour effects of propofol and local anaesthetics as well as pro- and anti-tumour effects following exposure to inhalational anaesthetics [ 19 , 20 , 21 , 22 , 23 ].…”

An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review

“…Shen et al (2021) showed that propofol could inhibit the proliferation, invasion and apoptosis of ovarian cancer cells through the lncRNA HOST2/JAK2/STAT3 axis. Chang et al (2022) reported that propofol exerted an antitumor effect by down-regulating lncRNA CAS9, thereby inhibiting the Akt/mTOR signaling pathway in hepatocellular carcinoma. In colon cancer, propofol promoted cell apoptosis and inhibited distant metastasis through the activation of WIF-1 and inhibition of Wnt signaling pathway by negatively regulating the expression of lncRNA HOTAIR (Zhang et al, 2020a).…”

Impact of propofol versus sevoflurane anesthesia on molecular subtypes and immune checkpoints of glioma during surgery

“…[10][11][12][13] Some anesthetic medications, including sevoflurane, dexmedetomidine, and propofol, may have some impact on the malignant phenotype of tumor cells. [14][15][16] These anesthetics are thought to be potential tumor suppressors or facilitators; however, it is still unknown how they will affect glioma patients. Sevoflurane and propofol are frequently used anesthetics in therapeutic settings.…”