Perioperative risk factors, including the choice of
anesthetics, may influence
ovarian cancer recurrence after surgery. Inhalational
anesthetic sevoflurane and intravenous agent
propofol might affect
cancer cell metabolism and signaling, which, in turn, may influence the
malignancy of
ovarian cancer cells. The different effects between
sevoflurane and
propofol on
ovarian cancer cell biology and underlying mechanisms were studied. Cultured
ovarian cancer cells were exposed to 2.5%
sevoflurane, 4 μg/mL
propofol, or
sham condition as the control for 2 h followed by 24-h recovery.
Glucose transporter 1 (GLUT1), mitochondrial
pyruvate carrier 1 (MPC1),
glutamate dehydrogenase 1 (GLUD1),
pigment epithelium-derived factor (PEDF), p-Erk1/2, and
hypoxia-inducible factor 1-alpha (HIF-1α) expressions were determined with immunostaining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to analyze metabolomics data.
Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression relative to the controls. In contrast to
sevoflurane,
propofol decreased GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α but increased PEDF expression.
Sevoflurane increased metabolite
isopropanol and decreased
glucose and
glutamine energy substrates in the media, but the opposite changes were found after
propofol treatment. Our data indicated that, unlike the pro-
tumor property of
sevoflurane,
propofol negatively modulated PEDF/Erk/HIF-1α cellular signaling pathway and inhibited
ovarian cancer metabolic efficiency and survival, and hence decreased
malignancy. The translational value of this work warrants further study. •
Sevoflurane promoted but
propofol inhibited
ovarian cancer cell biology. •
Sevoflurane upregulated but
propofol downregulated the GLUT1, MPC1, and GLUD1 expressions of
ovarian cancer cells. •
Sevoflurane enhanced but
propofol inhibited
ovarian cancer cellular
glucose. metabolism and glutaminolysis. •
Sevoflurane downregulated PEDF but upregulated the Erk pathway and HIF-1α, while
propofol had the adverse effects on
ovarian cancer cells.