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Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α.

Abstract：

PURPOSE:Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated. METHODS:A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting. RESULTS:Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia. CONCLUSIONS:Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

journal_name

J Anesth

journal_title

Journal of anesthesia

authors

Liang H,Yang CX,Zhang B,Wang HB,Liu HZ,Lai XH,Liao MJ,Zhang T

doi

10.1007/s00540-015-2035-7

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

821-30

issue

eissn

0913-8668

issn

1438-8359

pii

10.1007/s00540-015-2035-7

journal_volume

pub_type

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Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α.