Department of Anesthesia, Zhuhai Center for Maternal and Child Health Care, Zhuhai, China.
Department of Pharmacy, Zhuhai Center for Maternal and Child Health Care, Zhuhai, China.
Clin Exp Pharmacol Physiol. 2022 Feb;49(2):264-274. doi: 10.1111/1440-1681.13595. Epub 2021 Nov 9.
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.
异丙酚是一种广泛应用的短效静脉镇静剂，由于其具有肿瘤抑制作用和非麻醉作用，逐渐引起了人们的关注。代谢重编程功能障碍已被认为是肿瘤进展的一个有据可查的因素。本研究旨在探讨异丙酚对胃癌细胞多元醇途径的影响。在本研究中，我们发现异丙酚处理导致 BGC823 和 GES-1 细胞的细胞增殖显著下调，这归因于 AR 介导的多元醇途径减少。异丙酚刺激后，BGC823 和 GES-1 细胞中的醛酮还原酶家族 1 成员 B1 (AKR1B1) 和 AKR1B10 均显著降低，导致 AR 活性和山梨醇水平降低。添加山梨醇可以逆转异丙酚对细胞增殖的抑制作用。在机制上，异丙酚处理明显抑制核因子 (红系衍生 2)-样 2 (NRF2) 的磷酸化和核易位，随后降低 NRF2 与 AR 启动子的结合。用异丙酚处理的胃癌细胞中过表达 NRF2 可恢复 AR 表达。总之，这些发现表明，异丙酚通过 NRF2 介导的多元醇途径抑制 BGC823 和 GES-1 细胞的增殖，这将有助于为胃癌患者选择镇静剂。
