PMID- 34103583
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20211115
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jun 8
TI  - Hyperbaric oxygen suppressed tumor progression through the improvement of tumor 
      hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.
PG  - 12033
LID - 10.1038/s41598-021-91454-2 [doi]
LID - 12033
AB  - Tumor cells have long been recognized as a relative contraindication to 
      hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer 
      growth. However, in an oxygen deficit condition, tumor cells are more progressive 
      and can be metastatic. HBOT increasing in oxygen partial pressure may benefit 
      tumor suppression. In this study, we investigated the effects of HBOT on solid 
      tumors, such as lung cancer. Non-small cell human lung carcinoma 
      A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were 
      selected as an in vivo model to detect the potential mechanism of HBOT in lung 
      tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in 
      murine xenograft tumor models. Platelet endothelial cell adhesion molecule 
      (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved 
      caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were 
      aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the 
      growth of A549 cells in a time-dependent manner and immediately downregulated the 
      expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 
      protein could be rescued by a proteasome degradation inhibitor, but not an 
      autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved 
      tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer 
      cells in murine xenograft tumor models, through modifying the tumor hypoxic 
      microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment 
      for solid tumors, such as lung cancer.
FAU - Chen, Shao-Yuan
AU  - Chen SY
AD  - Department of Hyperbaric Medicine and Neurology, Cardinal Tien Hospital, New 
      Taipei City, Taiwan, ROC. 1sychen@yahoo.com.tw.
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC. 
      1sychen@yahoo.com.tw.
AD  - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical 
      Center, Taipei, Taiwan, ROC. 1sychen@yahoo.com.tw.
FAU - Tsuneyama, Koichi
AU  - Tsuneyama K
AD  - Department of Molecular and Environmental Pathology, The University of Tokushima, 
      Tokushima, Japan.
FAU - Yen, Mao-Hsiung
AU  - Yen MH
AD  - Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
FAU - Lee, Jiunn-Tay
AU  - Lee JT
AD  - Department of Neurology, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan, ROC.
FAU - Chen, Jiun-Liang
AU  - Chen JL
AD  - Department of Traditional Chinese Medicine, Chang Gung University, Taoyuan City, 
      Taiwan, ROC.
FAU - Huang, Shih-Ming
AU  - Huang SM
AD  - Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210608
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (PECAM1 protein, human)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - *Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/therapy
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Hyperbaric Oxygenation/*methods
MH  - Hypoxia
MH  - Immunohistochemistry
MH  - Lung Neoplasms/drug therapy/*therapy
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Transplantation
MH  - Neoplasms/*therapy
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - *Tumor Hypoxia
MH  - Tumor Microenvironment
PMC - PMC8187442
COIS- The authors declare no competing interests.
EDAT- 2021/06/10 06:00
MHDA- 2021/11/16 06:00
PMCR- 2021/06/08
CRDT- 2021/06/09 06:17
PHST- 2020/12/29 00:00 [received]
PHST- 2021/05/27 00:00 [accepted]
PHST- 2021/06/09 06:17 [entrez]
PHST- 2021/06/10 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/06/08 00:00 [pmc-release]
AID - 10.1038/s41598-021-91454-2 [pii]
AID - 91454 [pii]
AID - 10.1038/s41598-021-91454-2 [doi]
PST - epublish
SO  - Sci Rep. 2021 Jun 8;11(1):12033. doi: 10.1038/s41598-021-91454-2.