Abstract
Diabetes mellitus is associated with morbidity and progression of some cancers, such as hepatocellular carcinoma. It has been reported that sevoflurane, a volatile anesthetic agent commonly used in cancer surgery, can lead to lower overall survival rates than those observed when propofol is used to treat cancer patients, and sevoflurane increases cancer cell proliferation in in vitro studies. It has been also reported that glucose levels in rats anesthetized with sevoflurane were higher than those in rats anesthetized with propofol. We investigated the effect of sevoflurane, under conditions of high glucose and insulin, on cell proliferation in the human hepatocellular carcinoma cell line, HepG2. First, we exposed HepG2 cells to sevoflurane at 1 or 2 % concentration for 6 h in various glucose concentrations and then evaluated cell proliferation using the MTT assay. Subsequently, to mimic diabetic conditions observed during surgery, HepG2 cells were exposed to sevoflurane at 1 or 2 % concentration in high glucose concentrations at various concentrations of insulin for 6 h. One-percent sevoflurane exposure enhanced cell proliferation under conditions of high glucose, treated with 0.05 mg/l insulin. Our study implies that sevoflurane may affect cell proliferation in human hepatocellular carcinoma cells in a physiological situation mimicking that of diabetes.
This is a preview of subscription content, log in via an institution to check access.
References
Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, Li G, Wang L. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012;130:1639–48.
Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Nagata C, Mizoue T, Inoue M, Tsugane S, Sasazuki S. Diabetes mellitus and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2014;44:986–99.
Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, Zhang H, Li Z. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer. 2011;47:1928–37.
Enlund M, Berglund A, Andreasson K, Cicek C, Enlund A, Bergkvist L. The choice of anaesthetic—sevoflurane or propofol—and outcome from cancer surgery: a retrospective analysis. Ups J Med Sci. 2014;119:251–61.
Ecimovic P, McHugh B, Murray D, Doran P, Buggy DJ. Effects of sevoflurane on breast cancer cell function in vitro. Anticancer Res. 2013;33:4255–60.
Lucchinetti E, Zeisberger SM, Baruscotti I, Wacker J, Feng J, Zaugg K, Dubey R, Zisch AH, Vaugg M. Stem cell-like human endothelial progenitors show enhanced colony-forming capacity after brief sevoflurane exposure: preconditioning of angiogenic cells by volatile anesthetics. Anesth Analg. 2009;109:1117–26.
Sato K, Kitamura T, Kawamura G, Mori Y, Sato R, Araki Y, Yamada Y. Glucose use in fasted rats under sevoflurane anesthesia and propofol anesthesia. Anesth Analg. 2013;117:627–33.
Kitamura T, Sato K, Kawamura G, Yamada Y. The involvement of adenosine triphosphate-sensitive potassium channels in the different effects of sevoflurane and propofol on glucose metabolism in fed rats. Anesth Analg. 2012;114:110–6.
Benzonana LL, Perry NJ, Watts HR, Yang B, Perry IA, Coombes C, Takata M, Ma D. Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro. Anesthesiology. 2013;119:593–605.
Kawaraguchi Y, Horikawa YT, Murphy AN, Murray F, Miyanohara A, Ali SS, Head BP, Patel PM, Roth DM, Patel HH. Volatile anesthetics protect cancer cells against tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via caveolins. Anesthesiology. 2011;115:499–508.
Feng YH, Lin CY, Huang WT, Wu CL, Fang JL, Tsao CJ. Diabetes mellitus impairs the response to intra-arterial chemotherapy in hepatocellular carcinoma. Med Oncol. 2011;28:1080–8.
Kudoh A, Katagai H, Takazawa T. Sevoflurane increases glucose transport in skeletal muscle cells. Anesth Analg. 2002;95:123–8.
Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, Hoetzel A, Schmidt R, Borner C, Pahl H, Geiger K, Pannen BJ. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005;102:1147–57.
Matsuoka H, Kurosawa S, Horinouchi T, Kato M, Hashimoto Y. Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro. Anesthesiology. 2001;95:1467–72.
Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003;97:1331–9.
Kotani N, Hashimoto H, Sessler DI, Kikuchi A, Suzuki A, Takahashi S, Muraoka M, Matsuki A. Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia. Anesthesiology. 1998;89:1125–32.
Woods GM, Griffiths DM. Reversible inhibition of natural killer cell activity by volatile anaesthetic agents in vitro. Br J Anaesth. 1986;58:535–9.
Eisenstein TK, Hilburger ME. Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol. 1998;83:36–44.
Peterson PK, Molitor TW, Chao CC. Mechanisms of morphine-induced immunomodulation. Biochem Pharmacol. 1993;46:343–8.
Sacerdote P, Manfredi B, Mantegazza P, Panerai AE. Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol. 1997;121:834–40.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Nishiwada, T., Kawaraguchi, Y., Uemura, K. et al. Effect of sevoflurane on human hepatocellular carcinoma HepG2 cells under conditions of high glucose and insulin. J Anesth 29, 805–808 (2015). https://doi.org/10.1007/s00540-015-2025-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00540-015-2025-9