(C) and (D) Cell invasion assay demonstrated that loss of Nrf2 reversed the effect of propofol on invasion: propofol alone and propofol plus sh-NC significantly stimulated LOXO-101 mouse invasion, while propofol with ShRNA-1118 and ShRNA-2019 suppressed invasion in GBC-SD cells. Each experiment was performed three times in triplicate. * P < 0.05 vs. Control, # P < 0.05 vs. Propofol. Control: parental cells; Propofol: parental cells with propofol; NC + Propofol: cells transfected by ShNC incubated with propofol; 1118 + Propofol: cells transfected by ShRNA-1118 incubated with propofol; 2019 + Propofol: cells transfected by ShRNA-2019 incubated
with propofol. Discussion We evaluated effects of propofol on the behavior of human GC cells and the role of Nrf2 in these effects. Our study showed that propofol induced proliferation and invasion of gallbladder cancer cells through activation of Nrf2. Anesthesia represents one of the most important medical advances find more in history and is widely considered safe. Nevertheless, numerous anesthetics
are used for cancer resection even if their effect on the behavior of cancer cells is unclear . Propofol is one of these anesthetics. In in vivo experiments, different kinds of cancer cells treated by different concentrations of propofol showed divergent results. Garib et al. found that propofol (34 μmol/L) increased migration of MDA-MB-468 breast carcinoma cells . In contrast, Mammoto et al. demonstrated that clinically relevant concentrations of propofol (5.6-28 μmol/L) decreased the invasion ability of human cancer
cells (HeLa, HT1080, HOS and RPMI-7951) . Also, Miao et al. reported that propofol (at 45 μmol/L) Torin 1 nmr stimulation inhibited invasion of LOVO colon cancer cells . So we set a concentration range of propofol (0–40 μmol/L) to test its effect on the behavior of GBC-SD cells. Our results showed that propofol stimulation promoted proliferation by inhibiting apoptosis and increased the invasion ability. Nrf2 belongs to the cnc (“cap ‘n’ collar”) subfamily of the basic region leucine zipper transcription factors . Nrf2 is a critical factor regulating cellular defense response in many human pathological conditions. Upon exposure of cells to oxidative stress or chemopreventive compounds, Nrf2 translocates to the nucleus to Ergoloid activate transcription of several different types of genes, including those encoding endogenous antioxidants, phase II detoxifying enzymes, and transporters . As one of Nrf2 downstream target genes, HO-1 is an antioxidant enzyme that degrades prooxidant heme into ferrous iron, carbon monoxide, and biliverdin . HO-1 participates in the mechanisms for organ protection function effect of many intravenous and inhaled anesthetics including propofol . Since HO-1 is up-regulated by Nrf2 and propofol, we then investigated whether propofol had an effect on the activation of Nrf2.