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Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro.

Abstract：

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.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Zhang W,Sheng B,Chen S,Zhao H,Wu L,Sun Y,Cui J,Zhu X,Ma D

doi

10.1097/ALN.0000000000003129

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

1469-1481

issue

eissn

0003-3022

issn

1528-1175

pii

00000542-202006000-00029

journal_volume

132

pub_type

杂志文章

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Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro.