Propofol, a widely used intravenous anesthetic for induction and maintenance, modulates autophagy and exhibits anti-tumor or carcinogenic activity[1-2]. Propofol exerts its hypnotic actions by activating the central inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system[2]. In addition, Propofol possesses cyclooxygenase (COX)-inhibiting activity[3].
In vitro, exposure of H9c2 embryonal rat heart-derived cells to escalating concentrations of Propofol (12.5-100µmol/L) for 4h produced a dose-dependent, significant reduction in hypoxia/reoxygenation (H/R)-induced early-apoptotic cells while simultaneously elevating LC3-II levels in a dose-dependent manner. H/R alone reduced p62 protein abundance, and Propofol further amplified this H/R-induced decline in p62[4]. In neuronal PC12 cells, a 10min exposure to Propofol (10, 20, or 50µM) dose-dependently attenuated autophagy by down-regulating the autophagy-related proteins LC3-II, Beclin-1, and Beclin-1-phosphatidylinositol-3 kinase class III (class III PI3K)[5].
In vivo, in male Sprague-Dawley rats, continuous intravenous infusion of Propofol at 12mg/kg/h for 30min via the femoral vein markedly attenuated myocardial injury caused by ischemia–reperfusion (I/R) and significantly reduced the formation of cytosolic vacuoles and myofibrillar lysis in cardiomyocytes[6]. Nude mice received intraperitoneal injections of Propofol (35mg/kg) every 2 days for 14 days, resulting in significantly smaller pheochromocytoma (PCC) tumor volumes and weights and markedly enhanced tumor-cell apoptosis compared with the sham group[7].
References:
[1] Xu Y, Pan S, Jiang W, et al. Effects of propofol on the development of cancer in humans. Cell Prolif. 2020;53(8):e12867.
[2] Guo XN, Ma X. The Effects of Propofol on Autophagy. DNA Cell Biol. 2020;39(2):197-209.
[3] Inada T, Kubo K, Shingu K. Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol. J Anesth. 2011;25(4):569-575.
[4] Li H, Zhang X, Tan J, et al. Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury by inducing autophagy via the SAPK/JNK pathway. Mol Med Rep. 2018;17(3):4573-4580.
[5] Cui D, Wang L, Qi A, et al. Propofol prevents autophagic cell death following oxygen and glucose deprivation in PC12 cells and cerebral ischemia-reperfusion injury in rats [retracted in: PLoS One. 2022 Sep 28;17(9):e0275548. doi: 10.1371/journal.pone.0275548.]. PLoS One. 2012;7(4):e35324.
[6] Noh HS, Shin IW, Ha JH, et al. Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats. Mol Cells. 2010;30(5):455-460.
[7] Wang H, Zhang S, Zhang A, et al. Propofol Prevents the Progression of Malignant Pheochromocytoma In Vitro and In Vivo. DNA Cell Biol. 2018;37(4):308-315.
Propofol是一种广泛用于麻醉诱导和维持的静脉麻醉药，具有调节自噬、抗肿瘤或致癌活性[1-2]。Propofol的催眠作用主要通过激活中枢神经系统中的抑制性神经递质γ-氨基丁酸（GABA）而实现[2]。此外，Propofol还具有抑制环氧合酶（COX）的活性[3]。
在体外，将H9c2胚胎大鼠心肌源性细胞暴露于递增浓度的Propofol（12.5-100µmol/L）4小时，可剂量依赖性地显著减少缺氧/复氧（H/R）诱导的早期凋亡细胞，并同时以剂量依赖性方式提高LC3-II水平。H/R本身即可降低p62蛋白含量，而Propofol进一步增强了H/R引起的p62下降[4]。在神经元PC12细胞中，10分钟Propofol处理（10、20或50µM）可剂量依赖性地抑制自噬，表现为下调LC3-II、Beclin-1及Beclin-1-Ⅲ类磷脂酰肌醇-3-激酶（class III PI3K）等自噬相关蛋白[5]。
在体内，雄性Sprague-Dawley大鼠经股静脉持续静脉输注Propofol（12mg/kg/h，30分钟），显著减轻缺血再灌注（I/R）引起的心肌损伤，并明显减少心肌细胞胞质空泡和肌原纤维溶解[6]。裸鼠每2天腹腔注射Propofol（35mg/kg），持续14天，其嗜铬细胞瘤（PCC）肿瘤体积和重量显著小于假手术组，且肿瘤细胞凋亡显著增强[7]。