Abstract

The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P < 0.01) and volume (P < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after IH exposure. CIH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth.

Details

Title
Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer
Author
Kang, Hye Seon 1   VIAFID ORCID Logo  ; Young, Kwon Hee 1 ; Kim In Kyoung 1 ; Ban Woo Ho 1 ; Kim, Sei Won 1 ; Kang Hyeon Hui 1 ; Yeo Chang Dong 1 ; Haak, Lee Sang 2   VIAFID ORCID Logo 

1  The Catholic University of Korea, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224) 
2  The Catholic University of Korea, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224); The Catholic University of Korea, Cancer Research Institute, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-58906-7
ProQuest document ID
2351474403
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.