Newly Published
Perioperative Medicine  |   January 2020
Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro
Author Notes
  • From the Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China (W.Z., B.S., S.C., X.Z.); Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom (W.Z., H.Z., L.W., Y.S., J.C., D.M.); and the Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China (Y.S.)
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • X.Z. and D.M. contributed equally to this work.
    X.Z. and D.M. contributed equally to this work.×
  • Correspondence: Address correspondence to Dr. Ma: Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, United Kingdom. d.ma@imperial.ac.uk. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Pharmacology
Perioperative Medicine   |   January 2020
Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro
Anesthesiology Newly Published on January 28, 2020. doi:https://doi.org/10.1097/ALN.0000000000003129
Anesthesiology Newly Published on January 28, 2020. doi:https://doi.org/10.1097/ALN.0000000000003129
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Preclinical investigations have shown a variety effects of anesthetics on cancer cell biology

  • The effects of the volatile anesthetic sevoflurane on cervical cancer cells has not been previously reported

What This Article Tells Us That Is New:

  • Sevoflurane enhances the malignant potential of two immortalized cervical cancer cell lines in vitro

  • The underlying mechanisms include sevoflurane-induced increase in histone deacetylase 6, which, via changes in cellular cytoskeleton dynamics, may promote the invasive properties of cervical cancer cells

Background: Sevoflurane is commonly used for cervical cancer surgery, but its effect on cervical cancer cell biology remains unclear. This mechanistic study explores how sevoflurane affects the proliferation and metastatic potential of immortalized cervical cancer cell lines.

Methods: Cultured cervical cancer Caski and HeLa lines were exposed to 1, 2, or 3% sevoflurane for 2 or 4 h. Cell proliferation was determined through the Kit-8 assay and Ki-67 immunofluorescent staining. Cell migration and invasion were evaluated with the Transwell assay. Immunofluorescent staining and Western blot analysis were used to identify sevoflurane-induced morphological and biochemical changes.

Results: Sevoflurane exposure for either 2 or 4 h significantly increased HeLa cell proliferation in a time- and concentration-dependent manner to be 106 ± 2.7% and 107 ± 1.4% relative to the controls (n = 10; P = 0.036; P = 0.022) at 24 h after exposure and to be 106 ± 2.2% and 106 ± 1.7% relative to the controls (n = 10; P = 0.031; P = 0.023) at the highest concentration of 3% sevoflurane studied, respectively, but not Caski cells. Sevoflurane promoted invasion ability (1.63 ± 0.14 and 1.92 ± 0.12 relative to the controls) and increased cell size (1.69 ± 0.21 and 1.76 ± 0.13 relative to the controls) of Caski and HeLa cells (n = 6; all P < 0.001), respectively. Sevoflurane increased histone deacetylase 6 expression in both cells, and histone deacetylase 6 knockdown abolished the prometastatic effects of sevoflurane. Sevoflurane also induced deacetylation of α-tubulin in a histone deacetylase 6–dependent manner. The protein kinase B (AKT) or extracellular regulated protein kinase (ERK1/2) phosphorylation inhibition attenuated sevoflurane-induced histone deacetylase 6 expression.

Conclusions: Sevoflurane enhanced proliferation, migration, and invasion of immortalized cervical cancer cells, which was likely associated with increasing histone deacetylase 6 expression caused by phosphatidylinositide 3-kinase/AKT- and ERK1/2-signaling pathway activation.