Abstract
Propofol, a widely used short-acting intravenous sedative agent, has gradually gained attention due to the tumour-suppressing role and non-anaesthetic effect. Dysfunction of metabolic reprogramming has been recognised as a well-documented factor for tumour progression. The aim of this study is to explore the effect of propofol on the polyol pathway in gastric cancer cells. In this study, we found that propofol treatment led to a significant downregulation of cell proliferation in BGC823 and GES-1 cells, which was attributed to the decreased AR-mediated polyol pathway. Both aldo-keto reductase family 1, member B1 (AKR1B1) and AKR1B10 were significantly reduced in BGC823 and GES-1 cells in response to propofol stimulation, leading to decreased AR activity and sorbitol level. Addition of sorbitol could reverse the inhibitory effect of propofol on cell proliferation. Mechanically, propofol treatment drastically inhibited phosphorylation and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2), subsequently decreased the binding of NRF2 to AR promoter. Overexpression of NRF2 resulted in the recovery of AR expression in gastric cancer cell with propofol treatment. Taken together, these finding showed that propofol suppressed cell proliferation in BGC823 and GES-1 cell through NRF2-mediated polyol pathway, which would aid the selection of sedation for patients with gastric cancer.